This study aimed to assess the medicinal properties of Breynia retusa, a plant rich in phytocompounds predominantly used as an ethnomedicinal agent in Western Ghats, which appeared to be promising for therapeutic use, especially in the treatment of ovarian cancer. Herein, its cytotoxic potential on ovarian cancer cell lines SKOV-3, neurotoxicity, antioxidant activity, and molecular docking was determined to aid in explaining the mechanisms of interactions with proteins related to ovarian cancer. B . retusa methanolic extract demonstrated exuberant antioxidant activity, with 81.91% scavenging ability of DPPH radicals and efficient reduction of phosphomolybdenum (22.98 mg ascorbic acid equivalents antioxidant capacity/g extract). The extract proved to be an important anti-inflammatory agent through membrane stabilization inhibition of 83%. The cytotoxicity study against the SKOV-3 cell line indicated an IC50 value of 34.01 µg/mL and a very negligible neurotoxicity in SH-SY5Y cell lines. The GC-MS and HPLC profiling indicated many anticancer compounds in the extract such as secalciferol, methyl gallate, ricinoleic acid, gallic acid, and naringenin. The docking study showed significant interactions of secalciferol molecules with the key ovarian cancer proteins, which include IGF1 (-6.758 kcal/mol) and c-ERBB2 (-4.281 kcal/mol). Fatty acid derivatives and methyl gallate showed efficient dock scores (< -5.0 kcal/mol) with antioxidant (catalase and superoxide dismutase) enzymes and inflammatory cytokines (IL-6 and COX-1), respectively, as evidences of antioxidant and anti-inflammatory potentials. The bio-accessibility of phenolics and their antioxidant activity ranged above 90%, indicating the promising bioavailability of phytochemicals expected in vivo. Hence the current study emphasizes the anticancer potential of B. retusa phytocompounds that appeared to interact very strongly with ovarian cancer targets and confirms the dose-dependent cytotoxic and antioxidant activities of B. retusa methanolic extract.

The online version contains supplementary material available at 10.1007/s13205-025-04276-8.

Cancer treatments often exploit oxidative stress to selectively kill tumour cells by disrupting their lipid peroxidation membranes and inhibiting antioxidant enzymes. However, lipid peroxidation plays a dual role in cancer progression, acting as both a tumour promoter and a suppressor. Balancing oxidative stress through antioxidant therapy remains a challenge, as excessive antioxidant activity may compromise the efficacy of chemotherapy and radiotherapy.

This review explores the role of antioxidants in mitigating lipid peroxidation in cancer therapy while maintaining treatment efficacy. It highlights recent advancements in nanotechnology-based targeted antioxidant delivery to optimize therapeutic outcomes.

A comprehensive literature review was conducted using reputable databases, including PubMed, Scopus, Web of Science, and ScienceDirect. The search focused on publications from the past five years (2020-2025), supplemented by relevant studies from earlier years. Keywords such as "antioxidants," "lipid peroxidation," "nanotechnology in cancer therapy," and "oxidative stress" were utilized. Relevant articles were critically analysed, and graphical illustrations were created.

Emerging evidence suggests that nanoparticles, including liposomes, polymeric nanoparticles, metal-organic frameworks, and others, can effectively encapsulate and control the release of antioxidants in tumour cells while minimizing systemic toxicity. Stimuli-responsive carriers with tumour-specific targeting mechanisms further enhance antioxidant delivery. Studies indicate that these strategies help preserve normal cells, mitigate oxidative stress-related damage, and improve treatment efficacy. However, challenges such as bioavailability, stability, and potential interactions with standard therapies remain.

Integrating nanotechnology with antioxidant-based interventions presents a promising approach for optimizing cancer therapy. Future research should focus on refining lipid peroxidation modulation strategies, assessing oxidative stress profiles during treatment, and employing biomarkers to determine optimal antioxidant dosing. A balanced approach to antioxidant use may enhance therapeutic efficacy while minimizing adverse effects.

The development of innovative anticancer agents with minimal side effects is crucial. Polymeric Schiff bases have unique features that make them a promising option for therapeutic uses. They are well known for their biological properties, especially anticancer activity. Therefore, the current report describes the synthesis of Schiff bases derived from microcrystalline cellulose. Cellulose Schiff bases were synthesized through three steps. First, cellulose was periodate oxidized to produce dialdehyde cellulose (DAC). Afterwards, DAC was grafted with hyper-branched polyethylenimine (hPEI) to obtain aminated cellulose. Schiff bases were obtained by reacting hPEI-cellulose with various aldehydes. The final products were characterized by spectroscopic and thermal methods. The cellulose Schiff bases were evaluated for their anticancer activities, and it was observed that they were able to inhibit the growth of different types of cells. Importantly, one of the cellulose derivatives (SB4), which contains trimethoxy benzaldehyde moieties, was capable of inducing cell cycle arrest and apoptosis in hepatocellular carcinoma cells (Hep G2). Interestingly, SB4 could act as a pro-oxidant by inducing reactive oxygen species and oxidative stress with notable decline in the antioxidant system within Hep G2 cells. The results displayed that cellulose-based Schiff bases may offer a new strategy for liver cancer therapy.

Conventional thermoresponsive liposomes have failed to meet cancer targeting potential due to poor safety profile, unpredictable fate, and low therapeutic response in clinical studies. Recently, we reported phase-change nanostructured lipid carriers, termed thermoresponsive lipid nanoparticles (TLNs), for targeting cancer cells under hyperthermia. Herein, we have prepared ternary eutectic mixtures of myristic, stearic, and palmitic acid at a ratio of 2.5:1:1.5 yielded a melting point or solid-liquid phase transition temperature of 41°C. Doxorubicin (DOX)-loaded TLNs were fabricated and optimized using Box-Behnken Design Expert® software and exhibited desirable particle size (191.7±2.88 nm), polydispersity index (0.213±0.025), zeta-potential (-21.2±2.29 mV), spherical shape, high entrapment efficiency (92.24±1.05), and desirable physicochemical stability. In-vitro drug release studies showed hyperthermia-aided abrupt DOX release within 2 h at 41°C and 43°C while sustained drug release pattern for 12 h at 37°C. In-vitro cytotoxicity studies of TLN also exhibited the highest breast cancer (MCF-7) cells killing at hyperthermia (41°C), more than 3-fold compared to 37°C and free DOX solution. A 23-fold higher cell uptake in breast cancer cells further confirmed that ternary eutectic mixture-based DOX-loaded TLNs are an excellent candidate for breast cancer targeting and may be preferred over other nano-carriers due to the feasible preparation and superior stability.

Breast cancer's complexity and heterogeneity continue to present significant challenges in its treatment and management. Emerging research has underscored the pivotal role of microRNAs (miRNAs) in breast cancer pathogenesis, acting as crucial regulators of gene expression. This review delivers an in-depth analysis of miRNAs, highlighting their dual functions as both oncogenes and tumor suppressors, and detailing their impact on key biological processes, including cell proliferation, apoptosis, and metastasis. The mechanisms underlying miRNA action, particularly their interactions with target mRNAs and the factors influencing these dynamics, are thoroughly explored. Additionally, the review discusses the therapeutic prospects of miRNAs, with a focus on innovative delivery systems like nanoparticles that improve the stability and effectiveness of miRNA-based therapies. It also addresses the anticancer effects of natural compounds, such as genistein, hesperidin, quercetin, curcumin, resveratrol, epigallocatechin-3-gallate (EGCG), and glyceollins, which modulate miRNA expression and contribute to tumor growth inhibition. These advances seek to address the limitations of conventional therapies, paving the way for targeted interventions in breast cancer. By integrating current insights on miRNA biology, therapeutic strategies, and the potential of natural products to regulate miRNA expression, this review aims to shed light on miRNA- and natural product-based approaches as promising avenues for enhancing breast cancer treatment outcomes.

Taxol is widely used in cancer chemotherapy; however, the oral absorption of Taxol remains a formidable challenge. Since the intestinal p-glycoprotein (P-gp) mediated drug efflux is one of the primary causes, the development of P-gp inhibitor is emerging as a promising strategy to realize Taxol's oral delivery. Because P-gp exists in many tissues, the non-selective P-gp inhibitors would lead to toxicity. Correspondingly, a potent and intestine specific P-gp inhibitor would be an ideal solution to boost the oral absorption of Taxol and avoid exogenous toxicity. Herein, we would like to report a highly potent and intestine specific P-gp inhibitor to enable oral delivery of Taxol in high efficiency. Through a multicomponent reaction and post-modification, various benzofuran-fused-piperidine derivatives were achieved and the biological evaluation identified 16 c with potent P-gp inhibitory activity. Notably, 16 c was intestine specific and showed almost none absorption (F=0.82 %), but possessing higher efficacy than Encequidar to improve the oral absorption of Taxol. In MDA-MB-231 xenograft model, the oral administration of Taxol and 16 c showed high therapeutic efficiency and low toxicity, thus providing a valuable chemotherapy strategy.

The purpose of this study is to enhance the effectiveness of known anticancer medications using natural compounds. The study investigated the impact of combining AVE with PAX on non-small cell lung cancer (A549) and breast cancer (MCF7). In this study, A549 and MCF7 cells were treated with PAX (5 μM), AVE (24 μg/mL), and a combination of PAX and AVE (5 μM + 24 μg/mL). The glucose consumption rates of the cells were determined by extracellular acidification rate (ECAR) thanks to the SeaHorse XFe24 instrument. In addition, gene expression profiles were determined by performing Total RNA sequencing with the Novaseq 6000 instrument. Finally, the expressions of GAPDH, BAX, and BCL-2 genes involved in the apoptotic pathway were detected by RT-qPCR. The combined application of PAX and AVE reduced the ECAR value in both cell lines. According to the RT-qPCR results, the expression level of the apoptotic gene BAX increased in both cell lines (p < 0.05). Total RNA sequencing revealed that the combination effects of PAX and AVE play a role in the ribosome mechanism, thereby affecting the protein translation system in MCF7 while apoptosis and cell cycle have come to the forefront in A549.

Curcumin, a polyphenol natural product derived from turmeric, possesses diverse pharmacological effects due to its interactions with various cells and molecules. Recent studies have highlighted its immunomodulatory properties, including its impact on immune cells and mediators involved in immune responses. Th17 cells play a crucial role in promoting immune responses against extracellular pathogens by recruiting neutrophils and inducing inflammation. These cells produce inflammatory cytokines such as TNF-α, IL-21, IL-17A, IL-23, IL-17F, IL-22, and IL-26. Curcumin has been shown to significantly inhibit the proliferation of Th17 cells and reduce the production of inflammatory cytokines, including TNF-α, IL-22, and IL-17. This review aims to assess the effectiveness of curcumin and its underlying mechanisms in modulating Th17 cells.

Delivery systems based on albumin nanoparticles (NPs) have recently garnered substantial interest in anti-tumor drug development. However, systematic bibliometric analyses in this field remain lacking. This study aimed to analyze the current research status, hotspots, and frontiers in the application of albumin NPs in the field of oncology from a bibliometric perspective.

Using the Web of Science Core Collection (WOSCC) as the data source, retrieved articles were analyzed using software, such as VOSviewer 1.6.18 and CiteSpace 6.1.6, and the relevant visualization maps were plotted.

From 1 January 2000, to 15 April 2024, 2,262 institutions from 67 countries/regions published 1,624 articles related to the application of albumin NPs in the field of oncology. The USA was a leader in this field and held a formidable academic reputation. The most productive institution was the Chinese Academy of Sciences. The most productive author was Youn YS, whereas Kratz F was the most frequently co-cited author. The most productive journal was the International Journal of Nanomedicine, whereas the Journal of Controlled Release was the most co-cited journal. Future research hotspots and frontiers included "rapid and convenient synthesis methods predominated by self-assembly," "surface modification," "construction of multifunctional NPs for theranostics," "research on natural active ingredients mainly based on phenolic compounds," "combination therapy," and "clinical applications."

Based on our bibliometric analysis and summary, we obtained an overview of the research on albumin NPs in the field of oncology, identified the most influential countries, institutions, authors, journals, and citations, and discussed the current research hotspots and frontiers in this field. Our study may serve as an important reference for future research in this field.

Despite the considerable advancements in chemotherapy as a cornerstone modality in cancer treatment, the prevalence of complications and pre-existing diseases is on the rise among cancer patients along with prolonged survival and aging population. The relationships between these disorders and cancer are intricate, bearing significant influence on the survival and quality of life of individuals with cancer and presenting challenges for the prognosis and outcomes of malignancies. Herein, we review the prevailing complications and comorbidities that often accompany chemotherapy and summarize the lessons to learn from inadequate research and management of this scenario, with an emphasis on possible strategies for reducing potential complications and alleviating comorbidities, as well as an overview of current preclinical cancer models and practical advice for establishing bio-faithful preclinical models in such complex context.

The African continent is home to five biodiversity hotspots, boasting an immense wealth of medicinal flora, fungi and marine life. Diterpenes extracted from such natural products have compelling cytotoxic activities that warrant further exploration for the drug market, particularly in cancer therapy, where mortality rates remain elevated worldwide.

To demonstrate the potential of African natural products on the global stage for cancer therapy development and provide an in-depth analysis of the current literature on the activity of cancer cytotoxic diterpenes from African natural sources (to our knowledge, the first of its kind); not only to reveal the most promising candidates for clinical development, but to demonstrate the importance of preserving the threatened ecosystems of Africa.

A comprehensive search by means of the PRISMA strategy was conducted using electronic databases, namely Web of Science, PubMed, Google Scholar and ScienceDirect. The search terms employed were 'diterpene & mechanism & cancer' and 'diterpene & clinical & cancer'. The selection process involved assessing titles in English, Portuguese and Spanish, adhering to predefined eligibility criteria. The timeframe for inclusion spanned from 2010 to 2023, resulting in 218 relevant papers. Chemical structures were visualized using ChemDraw 21.0, PubChem was utilized to search for CID numbers.

Despite being one of the richest biodiverse zones in the world, African natural products are proportionally underreported compared to Asian countries or otherwise. The diterpenes andrographolide (Andrographis paniculata), forskolin (Coleus forskohlii), ent-kauranes from Isodon spp., euphosorophane A (Euphorbia sororia), cafestol & kahweol (Coffea spp.), macrocylic jolkinol D derivatives (Euphorbia piscatoria) and cyathane erinacine A (Hericium erinaceus) illustrated the most encouraging data for further cancer therapy exploration and development.

Diterpenes from African natural products have the potential to be economically significant active pharmaceutical and medicinal ingredients, specifically focussed on anticancer therapeutics.

Curcumin (Cur) is a phytochemical with various beneficial properties, including antioxidant, anti-inflammatory, and anticancer activities. However, its hydrophobicity, poor bioavailability, and stability limit its application in many biological approaches. In this study, a novel amphiphilic chitosan wall material was synthesized. The process was carried out via grafting chitosan with succinic anhydride (SA) as a hydrophilic group and deoxycholic acid (DA) as a hydrophobic group; 1H-NMR, FTIR, and XRD were employed to characterize the amphiphilic chitosan (CS-SA-DA). Using a low-cost, inorganic solvent-based procedure, CS-SA-DA was self-assembled to load Cur nanomicelles. This amphiphilic polymer formed self-assembled micelles with a core-shell structure and a critical micelle concentration (CMC) of 0.093 mg·mL-1. Cur-loaded nanomicelles were prepared by self-assembly and characterized by the Nano Particle Size Potential Analyzer and transmission electron microscopy (TEM). The mean particle size of the spherical Cur-loaded micelles was 770 nm. The drug entrapment efficiency and loading capacities were up to 80.80 ± 0.99% and 19.02 ± 0.46%, respectively. The in vitro release profiles of curcumin from micelles showed a constant release of the active drug molecule. Cytotoxicity studies and toxicity tests for zebrafish exhibited the comparable efficacy and safety of this delivery system. Moreover, the results showed that the entrapment of curcumin in micelles improves its stability, antioxidant, and anti-inflammatory activity.

In this extensive review work, the important role of AMP-activated protein kinase (AMPK) in causing of diabetes mellitus has been highlighted. Structural feature of AMPK as well its regulations and roles are described nicely, and the association of AMPK with the diabetic complications like nephropathy, neuropathy and retinopathy are also explained along with the connection between AMPK and β-cell function, insulin resistivity, mTOR, protein metabolism, autophagy and mitophagy and effect on protein and lipid metabolism.

Published journals were searched on the database like PubMed, Medline, Scopus and Web of Science by using keywords such as AMPK, diabetes mellitus, regulation of AMPK, complications of diabetes mellitus, autophagy, apoptosis etc.

After extensive review, it has been found that, kinase enzyme like AMPK is having vital role in management of type II diabetes mellitus. AMPK involve in enhance the concentration of glucose transporter like GLUT 1 and GLUT 4 which result in lowering of blood glucose level in influx of blood glucose into the cells; AMPK increases the insulin sensitivity and decreases the insulin resistance and further AMPK decreases the apoptosis of β-cells which result into secretion of insulin and AMPK is also involve in declining of oxidative stress, lipotoxicity and inflammation, owing to which organ damage due to diabetes mellitus can be lowered by activation of AMPK.

As AMPK activation leads to overall control of diabetes mellitus, designing and developing of small molecules or peptide that can act as AMPK agonist will be highly beneficial for control or manage diabetes mellitus.

The gut microbiota, known as the "forgotten organ" and "human second genome," comprises a complex microecosystem. It significantly influences the development of various tumors, including colorectal, liver, stomach, breast, and lung cancers, through both direct and indirect mechanisms. These mechanisms include the "gut-liver" axis, the "lung-intestine" axis, and interactions with the immune system. The intestinal flora exhibits dual roles in cancer, both promoting and suppressing its progression. Traditional Chinese medicine (TCM) can alter cancer progression by regulating the intestinal flora. It modifies the intestinal flora's composition and structure, along with the levels of endogenous metabolites, thus affecting the intestinal barrier, immune system, and overall body metabolism. These actions contribute to TCM's significant antitumor effects. Moreover, the gut microbiota metabolizes TCM components, enhancing their antitumor properties. Therefore, exploring the interaction between TCM and the intestinal flora offers a novel perspective in understanding TCM's antitumor mechanisms. This paper succinctly reviews the association between gut flora and the development of tumors, including colorectal, liver, gastric, breast, and lung cancers. It further examines current research on the interaction between TCM and intestinal flora, with a focus on its antitumor efficacy. It identifies limitations in existing studies and suggests recommendations, providing insights into antitumor drug research and exploring TCM's antitumor effectiveness. Additionally, this paper aims to guide future research on TCM and the gut microbiota in antitumor studies.

Individuals diagnosed with cancer often turn to the use of herbal remedies with the intention of treating and ameliorating the condition, impeding the progression of metastasis, enhancing immune function, mitigating stress, and inducing relaxation. Recently, medicinal plants were combined with conventional chemotherapy to decrease the side effects and increase the effectiveness of chemotherapy. This study showed the effectiveness of gemcitabine (Gem) was significantly increased after being used together with ethyl acetate extract obtained from Vernonia amygdalina (Eav) leaves. The combination doses of Eav and Gem were determined based on cytotoxic activity using the MTT assay method. The anticancer effect of this combination was identified by several parameters including the apoptosis effect, anti-migration, and anti-invasion activities of PANC-1 cells. Furthermore, this effect was explained via protein expression evaluation using immunohistochemical and flow cytometry. The Eav has a better Inhibitory Concentration 50 (IC50) than Gem of 21.19 ± 0.64 µg/mL and 164.78 ± 1.40 µg/mL. The combination of Eav and Gem at IC50 (1:1) has the strongest activity than Eav and Gem alone at 500.00 µg/mL. The anti-cancer effect of this combination showed significantly increased levels of apoptosis, particularly in the early phase of 17.46 ± 0.35 % (p < 0.0001) than Eav and Gem alone of 7.76 ± 0.25 % and 7.06 ± 0.20 %. A similar impact was evaluated in the migration and invasion of PANC-1 cells after the combination treatment. The % relative migration and cell invasion were significantly decreased compared to the control group and Eav or Gem alone by 21.49 ± 0.96 % and 125.25 ± 5.25 cells, respectively (p < 0.0001). This study found that signature molecules of VEGF, COX2, RAS, and MEK were down-regulated after treatment. Our study suggested that the Eav ameliorates the Gem effect against PANC-1 cells through apoptosis, migration, and invasion influence via RAS/MEK pathways.

Gastric cancer is the fifth most frequently diagnosed malignant neoplasm and the third leading cause of cancer-related mortality. Nevertheless, the therapeutic efficacy of conventional surgical and chemotherapeutic interventions in clinical practice is often unsatisfactory. Curcumin (Cur) has shown promise as a therapeutic agent in prior studies. However, its progress in this context has been impeded by challenges including low solubility, instability in aqueous environments, and rapid metabolism. In this study, we develop methacrylate fish gelatin (FGMA) hydrogel microparticles (FGMPs@Cur) encapsulating Cur via microfluidic electrospray technology for postoperative comprehensive treatment of gastric cancer. Comprehensive characterizations and analyses were conducted to assess the cytotoxicity against gastric cancer cells and potential tissue reparative effects of FGMPs@Cur. In vitro experiments revealed that FGMPs@Cur exhibited a remarkable cytotoxic effect on nearly 80 % of gastric cancer cells while maintaining at least 95 % viability of normal cells in cell compatibility tests. In vivo results demonstrated that FGMPs@Cur significantly reduced tumor volume to 47 % of the control group, and notable tissue regeneration was observed at the surgical site. These properties indicated that such a hydrogel microparticle system is a promising candidate for postoperative gastric cancer treatment in practical application.

Curcumin is a natural herb and polyphenol that is obtained from the medicinal plant Curcuma longa. It's anti-bacterial, anti-inflammatory, anti-cancer, anti-mutagenic, antioxidant and antifungal properties can be leveraged to treat a myriad of oral and systemic diseases. However, natural curcumin has weak solubility, limited bioavailability and undergoes rapid degradation, which severely limits its therapeutic potential. To overcome these drawbacks, nanocurcumin (nCur) formulations have been developed for improved biomaterial delivery and enhanced treatment outcomes. This novel biomaterial holds tremendous promise for the treatment of various oral diseases, the majority of which are caused by dental biofilm. These include dental caries, periodontal disease, root canal infection and peri-implant diseases, as well as other non-biofilm mediated oral diseases such as oral cancer and oral lichen planus. A number of in-vitro studies have demonstrated the antibacterial efficacy of nCur in various formulations against common oral pathogens such as S. mutans, P. gingivalis and E. faecalis, which are strongly associated with dental caries, periodontitis and root canal infection, respectively. In addition, some clinical studies were suggestive of the notion that nCur can indeed enhance the clinical outcomes of oral diseases such as periodontitis and oral lichen planus, but the level of evidence was very low due to the small number of studies and the methodological limitations of the available studies. The versatility of nCur to treat a diverse range of oral diseases augurs well for its future in dentistry, as reflected by rapid pace in which studies pertaining to this topic are published in the scientific literature. In order to keep abreast of the latest development of nCur in dentistry, this narrative review was undertaken. The aim of this narrative review is to provide a contemporaneous update of the chemistry, properties, mechanism of action, and scientific evidence behind the usage of nCur in dentistry.

Nanocarrier systems have been used in the study of esophageal cancer (EC) and other diseases, with significant advantages in improving the non-targeted and nonspecific toxicity of traditional formulations. Some chemotherapeutic drugs and high atomic number nanomaterials have sensitization effects on ionizing radiation and can be used as chemoradiation sensitizers.

Aurum (Au) nanoparticles were modified by bovine serum albumin (BSA) and folic acid (FA), and were core-loaded with paclitaxel (PTX) and curcumin (CUR). The basic characteristics of FA-BSA-Au@PTX/CUR nanomedicines were evaluated by transmission electron microscopy, Fourier transform infrared spectroscopy, and Malvern Zetasizer. The encapsulation and release of drugs were monitored by ultraviolet-visible spectrophotometry (UV-Vis). The biological toxicity and radiotherapy sensitization effect of FA-BSA-Au@PTX/CUR were observed by cell viability, colony formation, cell apoptosis, cell cycle distribution, and γ-H2AX analysis experiments.

The prepared nanomedicines showed good stability and spherical morphology. The results of cell uptake and cell viability detection revealed that FA-BSA-Au@PTX/CUR could specifically target EC cell KYSE150 and exert a certain inhibitory effect on proliferation, with no obvious toxicity on healthy cells Het-1A. In addition, the results of the colony formation experiment, cell apoptosis detection, cell cycle distribution, and γ-H2AX analysis showed that compared with X-rays alone, FA-BSA-Au@PTX/CUR combined with X-rays exhibited relatively stronger radiotherapy sensitization and anti-tumor activity.

FA-BSA-Au@PTX/CUR could target EC cancer cells and act as a safe and effective radiotherapy sensitizer to improve the radiotherapy efficacy of EC.

The treatment of breast cancer relies heavily on chemotherapy, but chemotherapy is limited by the disadvantages of poor targeting, susceptibility to extracellular matrix (ECM) interference and a short duration of action in tumor cells. To address these limitations, we developed an amphipathic peptide containing an RGD motif, Pep1, that encapsulated paclitaxel (PTX) and losartan potassium (LP) to form the drug-loaded peptide PL/Pep1. PL/Pep1 self-assembled into spherical nanoparticles (NPs) under normal physiological conditions and transformed into aggregates containing short nanofibers at acidic pH. The RGD peptide facilitated tumor targeting and the aggregates prolonged drug retention in the tumor, which allowed more drug to reach and accumulate in the tumor tissue to promote apoptosis and remodel the tumor microenvironment. The results of in vitro and in vivo experiments confirmed the superiority of PL/Pep1 in terms of targeting, prolonged retention and facilitated penetration for antitumor therapy. In conclusion, amphipathic peptides as coloaded drug carriers are a new platform and strategy for breast cancer chemotherapy.

Glioblastoma is a type of intracranial malignancy. Shikonin, a Chinese traditional medicine, has been shown to have anti-tumor efficacy toward human glioblastoma cells in vitro. However, shikonin cannot easily cross the blood-brain barrier. To address this issue, we evaluated the anti-tumor effects of direct intracranial infusion of shikonin in in vivo orthotopic syngeneic murine glioblastoma models using C57BL/6 mice.

The cytotoxic effects of shikonin against murine glioblastoma cells, SB28 and CT-2A, were reported resistance to temozolomide, were evaluated using an allophycocyanin-conjugated annexin V and propidium iodide assay with flow cytometry. Impedance-based real-time cell analysis (RTCA) was used to analyze the inhibitory effects of shikonin on growth and proliferation. To evaluate the anti-tumor activity of shikonin in vivo, we used orthotopic syngeneic murine glioblastoma models with SB28 and CT-2A cells.

In flow cytometry-based cytotoxic assays, shikonin induced apoptosis. RTCA indicated that shikonin decreased the cell index of murine glioblastoma cells, SB28 and CT-2A, in a dose-dependent manner (p < 0.0001 for both cell lines), while temozolomide did not (p = 0.91 and 0.82, respectively). In murine glioblastoma models, SB28 and CT-2A, direct intracranial infusion of shikonin, as a local chemotherapy, improved the overall survival of mice in a dose-dependent manner compared with control groups (p < 0.0001 and p = 0.02, respectively). While temozolomide did not (p = 0.48 and 0.52, respectively).

The direct intracranial infusion of shikonin has potential as a local therapy for patients with glioblastoma.

Although chemotherapy drugs are extensively utilized in cancer therapy, their administration for treatment of patients has faced problems that regardless of chemoresistance, increasing evidence has shown concentration-related toxicity of drugs. Doxorubicin (DOX) is a drug used in treatment of solid and hematological tumors, and its function is based on topoisomerase suppression to impair cancer progression. However, DOX can also affect the other organs of body and after chemotherapy, life quality of cancer patients decreases due to the side effects. Heart is one of the vital organs of body that is significantly affected by DOX during cancer chemotherapy, and this can lead to cardiac dysfunction and predispose to development of cardiovascular diseases and atherosclerosis, among others. The exposure to DOX can stimulate apoptosis and sometimes, pro-survival autophagy stimulation can ameliorate this condition. Moreover, DOX-mediated ferroptosis impairs proper function of heart and by increasing oxidative stress and inflammation, DOX causes cardiac dysfunction. The function of DOX in mediating cardiac toxicity is mediated by several pathways that some of them demonstrate protective function including Nrf2. Therefore, if expression level of such protective mechanisms increases, they can alleviate DOX-mediated cardiac toxicity. For this purpose, pharmacological compounds and therapeutic drugs in preventing DOX-mediated cardiotoxicity have been utilized and they can reduce side effects of DOX to prevent development of cardiovascular diseases in patients underwent chemotherapy. Furthermore, (nano)platforms are used comprehensively in treatment of cardiovascular diseases and using them for DOX delivery can reduce side effects by decreasing concentration of drug. Moreover, when DOX is loaded on nanoparticles, it is delivered into cells in a targeted way and its accumulation in healthy organs is prevented to diminish its adverse impacts. Hence, current paper provides a comprehensive discussion of DOX-mediated toxicity and subsequent alleviation by drugs and nanotherapeutics in treatment of cardiovascular diseases.

Paclitaxel is a natural anticancer compound with minimal toxicity, the capacity to stabilize microtubules, and high efficiency that has remained the standard of treatment alongside platinum-based therapy as a remedy for a variety of different malignancies. In contrast, polyphenols such as flavonoids are also efficient antioxidant and anti-inflammatory and have now been shown to possess potent anticancer properties. Therefore, the synergistic effects of paclitaxel and flavonoids against cancer will be of interest. In this review, we use a Boolean query to comprehensively search the well-known Scopus database for literature research taking the advantage of paclitaxel and flavonoids simultaneously while treating various types of cancer. After retrieving and reviewing the intended investigations based on the input keywords, the anticancer mechanisms of flavonoids and paclitaxel and their synergistic effects on different targets raging from cell lines to animal models are discussed in terms of the corresponding involved signaling transduction. Most studies demonstrated that these signaling pathways will induce apoptotic / pro-apoptotic proteins, which in turn may activate several caspases leading to apoptosis. Finally, it can be concluded that the results of this review may be beneficial in serving as a theoretical foundation and reference for future studies of paclitaxel synthesis, anticancer processes, and clinical applications involving different clinical trials.

This study examines the potential anticancer properties of curcumin carbon nanodot-decorated chitosan nanoparticles (CCM@CD/CS-NP) in HepG2 hepatocellular carcinoma cells. CCM@CD/CS-NPs were synthesized, and their size, morphology, and elemental analysis were characterized. The combination of curcumin carbon dots and chitosan in the form of a nanoparticle has a number of benefits, including improved solubility and bioavailability of curcumin, enhanced stability and biocompatibility of carbon dots, and sustained release of the drug due to the mucoadhesive properties of chitosan. The purpose of this research was to examine the efficacy of curcumin carbon dot-decorated chitosan nanoparticles as an anticancer agent in the treatment of HepG2 cell lines. The cell proliferation and apoptosis-related gene expressions in HepG2 cells were assessed to investigate the potential use of nanoparticles in vitro. The IC50 value for the inhibitory effect of CCM@CD/CS-NPs on cell growth and proliferation was determined to be 323.61 μg/mL at 24 h and 267.73 μg/mL at 48 h. Increased caspase-3 and -9 activation shows that CCM@CD/CS-NPs promoted apoptosis in HepG2 cells. It was also shown that the overexpression of Bax and the downregulation of Bcl-2 were responsible for the apoptotic impact of CCM@CD/CS-NPs. The nanoparticles have been shown to have minimal toxicity to normal liver cells, indicating their potential as a safe and effective treatment for HepG2. These novel nanomaterials effectively suppressed tumor development and boosted the rate of apoptotic cell death.

A growing body of evidence indicates that the anticancer effect of the immune system can be activated by the immunogenic modulation of dying cancer cells. Cancer cell death, as a result of the activation of an immunomodulatory response, is called immunogenic cell death (ICD). This regulated cell death occurs because of increased immunogenicity of cancer cells undergoing ICD. ICD plays a crucial role in stimulating immune system activity in cancer therapy. ICD can therefore be an innovative route to improve anticancer immune responses associated with releasing damage-associated molecular patterns (DAMPs). Several conventional and chemotherapeutics, as well as preclinically investigated compounds from natural sources, possess immunostimulatory properties by ICD induction. Natural compounds have gained much interest in cancer therapy owing to their low toxicity, low cost, and inhibiting cancer cells by interfering with different mechanisms, which are critical in cancer progression. Therefore, identifying natural compounds with ICD-inducing potency presents agents with promising potential in cancer immunotherapy. Naturally derived compounds are believed to act as immunoadjuvants because they elicit cancer stress responses and DAMPs. Acute exposure to DAMP molecules can activate antigen-presenting cells (APCs), such as dendritic cells (DCs), which leads to downstream events by cytotoxic T lymphocytes (CTLs) and natural killer cells (NKs). Natural compounds as inducers of ICD may be an interesting approach to ICD induction; however, parameters that determine whether a compound can be used as an ICD inducer should be elucidated. Here, we aimed to discuss the impact of multiple ICD inducers, mainly focusing on natural agents, including plant-derived, marine molecules, and bacterial-based compounds, on the release of DAMP molecules and the activation of the corresponding signaling cascades triggering immune responses. In addition, the potential of synthetic agents for triggering ICD is also discussed.

Polymer-drug conjugates (PDCs) have shown great promise in enhancing the efficacy and safety of cancer therapy. These conjugates combine the advantageous properties of both polymers and drugs, leading to improved pharmacokinetics, controlled drug release, and targeted delivery to tumor tissues. This review provides a comprehensive overview of recent developments in PDCs for cancer therapy. First, various types of polymers used in these conjugates are discussed, including synthetic polymers, such as poly(↋-caprolactone) (PCL), D-α-tocopheryl polyethylene glycol (TPGS), and polyethylene glycol (PEG), as well as natural polymers such as hyaluronic acid (HA). The choice of polymer is crucial to achieving desired properties, such as stability, biocompatibility, and controlled drug release. Subsequently, the strategies for conjugating drugs to polymers are explored, including covalent bonding, which enables a stable linkage between the polymer and the drug, ensuring controlled release and minimizing premature drug release. The use of polymers can extend the circulation time of the drug, facilitating enhanced accumulation within tumor tissues through the enhanced permeability and retention (EPR) effect. This, in turn, results in improved drug efficacy and reduced systemic toxicity. Moreover, the importance of tumor-targeting ligands in PDCs is highlighted. Various ligands, such as antibodies, peptides, aptamers, folic acid, herceptin, and HA, can be incorporated into conjugates to selectively deliver the drug to tumor cells, reducing off-target effects and improving therapeutic outcomes. In conclusion, PDCs have emerged as a versatile and effective approach to cancer therapy. Their ability to combine the advantages of polymers and drugs offers enhanced drug delivery, controlled release, and targeted treatment, thereby improving the overall efficacy and safety of cancer therapies. Further research and development in this field has great potential to advance personalized cancer treatment options.

The glycolysis is a common characteristic of cancer and it is responsible for providing enough energy to ensure growth. The glycolysis suppression is beneficial in tumor growth reduction. The stimulation/inhibition of glycolysis in cancer is tightly regulated by ncRNAs. The regulation of glycolysis by ncRNAs can influence proliferation and therapy response of tumor. The miRNAs are capable of inactivating enzymes responsible for glycolysis and suppressing signaling networks resulting in glycolysis induction. By regulation of glycolysis, miRNAs can affect therapy response. The lncRNAs and circRNAs follow a same pathway and by targeting glycolysis, they affect progression and therapy response of tumor. Noteworthy, lncRNAs and circRNAs sponge miRNAs in glycolysis mechanism control in tumor cells. Furthermore, ncRNA-mediated regulation of glycolysis mechanism can influence metastasis to organs of body. The ncRNAs regulating glycolysis are reliable biomarkers in cancer patients and more importantly, exosomal ncRNAs due to their presence in body fluids, are minimally-invasive biomarkers.

Atriplex hortensis var. rubra L. extracts prepared from leaves, seeds with sheaths, and stems were characterized for betalainic profiles by spectrophotometry, LC-DAD-ESI-MS/MS and LC-Orbitrap-MS techniques. The presence of 12 betacyanins in the extracts was strongly correlated with high antioxidant activity measured by ABTS, FRAP, and ORAC assays. Comparative assessment between samples indicated the highest potential for celosianin and amaranthin (IC₅₀ 21.5 and 32.2 μg/ml, respectively). The chemical structure of celosianin was elucidated for the first time by complete 1D and 2D NMR analysis. Our findings also demonstrate that betalain-rich A. hortensis extracts and purified pigments (amaranthin and celosianin) do not induce cytotoxicity in a wide concentration range in rat cardiomyocytes model (up to 100 μg/ml for extracts and 1 mg/ml for pigments). Furthermore, tested samples effectively protect H9c2 cells from H₂O₂-induced cell death and prevent from apoptosis induced by Paclitaxel. The effects were observed at sample concentrations between 0.1 and 10 μg/ml.

Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.

Colorectal cancer (CRC) is a dangerous form of cancer that affects the gastrointestinal tract. It is a major global health concern, and the aggressive behavior of tumor cells makes it difficult to treat, leading to poor survival rates for patients. One major challenge in treating CRC is the metastasis, or spread, of the cancer, which is a major cause of death. In order to improve the prognosis for patients with CRC, it is necessary to focus on ways to inhibit the cancer's ability to invade and spread. Epithelial-mesenchymal transition (EMT) is a process that is linked to the spread of cancer cells, also known as metastasis. The process transforms epithelial cells into mesenchymal ones, increasing their mobility and ability to invade other tissues. This has been shown to be a key mechanism in the progression of colorectal cancer (CRC), a particularly aggressive form of gastrointestinal cancer. The activation of EMT leads to increases in the spread of CRC cells, and during this process, levels of the protein E-cadherin decrease while levels of N-cadherin and vimentin increase. EMT also contributes to the development of resistance to chemotherapy and radiation therapy in CRC. Non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a role in regulating EMT in CRC, often through their ability to "sponge" microRNAs. Anti-cancer agents have been shown to suppress EMT and reduce the progression and spread of CRC cells. These findings suggest that targeting EMT or related mechanisms may be a promising approach for treating CRC patients in the clinic.

Prostate cancer is among most malignant tumors around the world and this urological tumor can be developed as result of genomic mutations and their accumulation during progression towards advanced stage. Due to lack of specific symptoms in early stages of prostate cancer, most cancer patients are diagnosed in advanced stages that tumor cells display low response to chemotherapy. Furthermore, genomic mutations in prostate cancer enhance the aggressiveness of tumor cells. Docetaxel and paclitaxel are suggested as well-known compounds for chemotherapy of prostate tumor and they possess a similar function in cancer therapy that is based on inhibiting depolymerization of microtubules, impairing balance of microtubules and subsequent delay in cell cycle progression. The aim of current review is to highlight mechanisms of paclitaxel and docetaxel resistance in prostate cancer. When oncogenic factors such as CD133 display upregulation and PTEN as tumor-suppressor shows decrease in expression, malignancy of prostate tumor cells enhances and they can induce drug resistance. Furthermore, phytochemicals as anti-tumor compounds have been utilized in suppressing chemoresistance in prostate cancer. Naringenin and lovastatin are among the anti-tumor compounds that have been used for impairing progression of prostate tumor and enhancing drug sensitivity. Moreover, nanostructures such as polymeric micelles and nanobubbles have been utilized in delivery of anti-tumor compounds and decreasing risk of chemoresistance development. These subjects are highlighted in current review to provide new insight for reversing drug resistance in prostate cancer.

Since the first report on the pharmacological activity of curcumin in 1949, enormous amounts of research have reported diverse activities for this natural polyphenol found in the dietary spice turmeric. However, curcumin has not yet been used for human application as an approved drug. The clinical translation of curcumin has been hampered due to its low solubility and bioavailability. The improvement in bioavailability and solubility of curcumin can be achieved by its formulation using drug delivery systems. Hydrogels with their biocompatibility and low toxicity effects have shown a substantial impact on the successful formulation of hydrophobic drugs for human clinical trials. This review focuses on hydrogel-based delivery systems for curcumin and describes its applications as anti-cancer as well as wound healing agents.

Prostate cancer (PCa) represents the fifth cause of cancer death in men. Currently, chemotherapeutic agents for the treatment of cancers, including PCa, mainly inhibit tumor growth by apoptosis induction. However, defects in apoptotic cellular responses frequently lead to drug resistance, which is the main cause of chemotherapy failure. For this reason, trigger non-apoptotic cell death might represent an alternative approach to prevent drug resistance in cancer. Several agents, including natural compounds, have been shown to induce necroptosis in human cancer cells. In this study we evaluated the involvement of necroptosis in anticancer activity of delta-tocotrienol (δ-TT) in PCa cells (DU145 and PC3). Combination therapy is one tool used to overcome therapeutic resistance and drug toxicity. Evaluating the combined effect of δ-TT and docetaxel (DTX), we found that δ-TT potentiates DTX cytotoxicity in DU145 cells. Moreover, δ-TT induces cell death in DU145 cells that have developed DTX resistance (DU-DXR) activating necroptosis. Taken together, obtained data indicate the ability of δ-TT to induce necroptosis in both DU145, PC3 and DU-DXR cell lines. Furthermore, the ability of δ-TT to induce necroptotic cell death may represent a promising therapeutical approach to overcome DTX chemoresistance in PCa.

Cancer is one of the acute life-threatening diseases endangering the whole of humanity. The treatment modalities for cancer are various. However, in most cases, a single treatment choice provides multiple side effects, poor targeting, and ineffective treatment. In recent years, the physiological regulatory function of carbon monoxide (CO) in the cancer process has been reported gradually, and CO-related nano-drugs have been explored. It shows better application prospects in cancer treatment and provides new ideas for treatment. The present review introduces the pathophysiological role of CO. The recent advances in cancer therapy, such as CO-mediated gas therapy, combined application of CO chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and immunotherapy, are described. Current challenges and future developments in CO-based treatment are also discussed. This review provides comprehensive information on recent advances in CO therapy and also some valuable guidance for promoting the progress of gas therapy nanomedicine.

Paclitaxel is a primary chemotherapy agent that displays antitumor activity against a variety of solid tumors. However, the clinical effectiveness of the drug is hampered by its nephrotoxic and cardiotoxic side effects. Thus, this investigation aimed at assessing the protective effects of rutin, hesperidin, and their combination to alleviate nephrotoxicity caused by paclitaxel (Taxol), cardiotoxicity in male Wistar rats, as well as oxidative stress. Rutin (10 mg/kg body weight), hesperidin (10 mg/kg body weight), and their mixture were given orally every other day for six weeks. Rats received intraperitoneal injections of paclitaxel twice weekly, on the second and fifth days of the week, at a dose of 2 mg/kg body weight. In paclitaxel-treated rats, the treatment of rutin and hesperidin decreased the elevated serum levels of creatinine, urea, and uric acid, indicating a recovery of kidney functions. The cardiac dysfunction in paclitaxel-treated rats that got rutin and hesperidin treatment also diminished, as shown by a substantial reduction in elevated CK-MB and LDH activity. Following paclitaxel administration, the severity of the kidney and the heart's histopathological findings and lesion scores were markedly decreased by rutin and hesperidin administration. Moreover, these treatments significantly reduced renal and cardiac lipid peroxidation while markedly increased GSH content and SOD and GPx activities. Thus, paclitaxel likely induces toxicity in the kidney and the heart by producing oxidative stress. The treatments likely countered renal and cardiac dysfunction and histopathological changes by suppressing oxidative stress and augmenting the antioxidant defenses. Rutin and hesperidin combination was most efficacious in rescuing renal and cardiac function as well as histological integrity in paclitaxel-administered rats.

We examined the photodynamic activation of Curcumin under blue light in glioblastoma T98G cells. The therapeutic effect of Curcumin, in both the absence and presence of blue light, was measured by the MTT assay and apoptosis progression using flow cytometry. Fluorescence imaging was carried out to evaluate Curcumin uptake. Photodynamic activation of Curcumin (10 µM), in the presence of blue light, enhanced its cytotoxic effect, resulting in the activation of ROS-dependent apoptotic pathways in T98G cells. The gene expression studies showed the expression of matrixes metalloproteinase 2 (MMP2) and 9 (MMP9) decrease with Curcumin (10 µM) under blue light exposure, indicating possible proteolytic mechanisms. Moreover, the cytometric appearance displayed that the expressions of NF-κB and Nrf2 were found to be increased upon exposure to blue light, which revealed a significant induction of expression of nuclear factor as a result of blue-light-induced oxidative stress and cell death. These data further demonstrate that Curcumin exhibited a photodynamic effect via induction of ROS-mediated apoptosis in the presence of blue light. Our results suggest that the application of blue light enhances the therapeutic efficacy of Curcumin in glioblastoma because of the phototherapeutic effect.

In this study, we established a simple and rapid in vitro method for screening multidrug resistance (MDR) reversal agents in traditional Chinese medicines (TCMs), which could better correspond to the MDR reversing effect in vivo. Here, D-luciferin, a substrate for the enzyme firefly luciferase and also a substrate for ATP-binding cassette transporters (ABC transporters), was used as the probe to detect its efflux kinetics caused by ABC transporters. First, we established a stable doxorubicin (DOX)-resistant cell line (MCF-7/DOX^Fluc) that overexpressed luciferase. Then, some kinds of TCMs were chosen for the MDR reversal agents to measure its effect on inhibiting the D-luciferin outflow from MCF-7/DOX^Fluc, and the ideal reversal agent with the least D-luciferin efflux from MCF-7/DOX^Fluc was selected to further investigate its effect combined with DOX on MCF-7/DOX^Fluc tumor-bearing mice. The results indicated that quercetin (Qu) could remarkably increase the retention of D-luciferin in MCF-7/DOX^Fluc in vitro and in vivo. Also, the combination of Qu and DOX could exceedingly inhibit the tumor growth, which proved the feasibility of this in vitro screening method. The study proposed a feasible method for mass screening of MDR agents from TCMs in vitro.

Plant-derived bioactive compounds are gaining wide attention for their multiple health-promoting activities and in particular for their anti-cancer properties. Several studies have highlighted how they can prevent cancer initiation and progression, improve the effectiveness of chemotherapy, and, in some cases, limit some of the side effects of chemotherapy agents. In this paper, we provide an update of the literature on the anti-cancer effects of three extensively studied plant-derived compounds, namely resveratrol, epigallocatechin gallate, and curcumin, with a special focus on the anti-cancer molecular mechanisms inducing apoptosis in the major types of cancers globally.

Nicotinamide N-methyltransferase (NNMT) and Dickkopf-1 (DKK1) play an important role in the development of breast cancer, and the purpose of this study was designed to examine the clinical and prognostic significance of NNMT and DKK1 in breast cancer.

The GEPIA2 database was used to evaluate the expression and survival of NNMT mRNA and DKK1 mRNA of breast cancer. Then an immunohistochemical study was carried out on 374 cases of breast tissue to identify the protein expression and significance of NNMT and DKK1. Next, the prognostic significance of DKK1 in breast cancer was explored by COX and Kaplan-Meier models.

Protein NNMT expression was correlated with lymph node metastasis and histological grade (P < .05) while protein DKK1 expression was related to tumor size, pT stage, histological grade, and Ki-67 (P < .05). Protein DKK1 was related to disease-specific survival (DSS), and low DKK1 expression indicated a poor prognosis of breast cancer patients (P < .05). Combined expression of protein NNMT and protein DKK1 predicted different prognosis of DSS (P < .05).

Nicotinamide N-methyltransferase and DKK1 were linked to breast cancer malignancy and invasion. Breast cancer patients with low DKK1 expression had a worse prognosis. Oncotypes of NNMT and DKK1 expression predicted patient outcomes.

Despite the advances made in cancer treatment in the past decades, therapeutic efficacy is still quite challenging, partially due to the emergence of multidrug resistance (MDR). It is crucial to decipher the underlying mechanisms of resistance in order to develop new therapeutic strategies for cancer patients. Previous studies have shown that activation of nuclear factor-κB (NF-κB) plays key roles in various cellular processes including proliferation, anti-apoptosis, metastasis, invasion, and chemoresistance.

In this review, we conduct an integrated analysis of the evidence suggesting the vital roles of the NF-κB signaling pathway in MDR during chemotherapy, immunotherapy, endocrine, and targeted therapy. A literature search was performed on NF-κB and drug resistance in PubMed up to February 2023.

This review summarizes that the NF-κB signaling pathway exhibits a crucial role in enhancing drug resistance in chemotherapy, immunotherapy, endocrine, and targeted therapy. The application of combination therapy with existing antineoplastic drugs and a safe NF-κB inhibitor could become a promising strategy in cancer treatment. A better understanding of the pathway and mechanisms of drug resistance may help exploit safer and more effective NF-κB-targeting agents for clinical use in the future.

Liver is an important organ in body that performs vital functions such as detoxification. Liver is susceptible to development of cancers, and hepatocellular carcinoma (HCC) is among them. 75-85% of liver cancer cases are related to HCC. Therefore, much attention has been directed towards understanding factors mediating HCC progression. LncRNAs are epigenetic factors with more than 200 nucleotides in length located in both nucleus and cytoplasm and they are promising candidates in cancer therapy. Directing studies towards understanding function of lncRNAs in HCC is of importance. LncRNAs regulate cell cycle progression and growth of HCC cells, and they can also induce/inhibit apoptosis in tumor cells. LncRNAs affect invasion and metastasis in HCC mainly by epithelial-mesenchymal transition (EMT) mechanism. Revealing the association between lncRNAs and downstream signaling pathways in HCC is discussed in the current manuscript. Infectious diseases can affect lncRNA expression in mediating HCC development and then, altered expression level of lncRNA is associated with drug resistance and radio-resistance. Biomarker application of lncRNAs and their role in prognosis and diagnosis of HCC are also discussed to pave the way for treatment of HCC patients.

The present study aimed to construct a co-loading platform encapsulating curcumin and paclitaxel at ratios of 2:1-80:1 (w/w) designated "CU-PTX-LNP" and explored the synergistic effects of CU-PTX at different composite proportions on liver cancer cells using the combination index (CI) method.

The CU lipid nanoplatform (CU-LNP) formulation was optimized via single-factor and orthogonal experiments. Various concentrations of PTX were added to the optimal formulation of CU-LNP to generate CU-PTX-LNP and the nanoplatform characterized via differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD), zeta potential, polydispersity index (PDI), and size analyses. The cumulative release, stability, and cytotoxicity of CU-PTX-LNP in LO2, HepG2, and SMMC-7221 cells were assessed in vitro, followed by safety investigation and pharmacokinetic studies in vivo. The anti-tumor activity of CU-PTX-LNP was also evaluated using nude mice.

CU-PTX-LNP formulations containing CU:PTX at a range of proportions (2:1-80:1; w/w) appeared as uniformly dispersed nanosized spherical particles with high entrapment efficiency (EE> 90%), sustained release and long-lasting stability. Data from in vitro cytotoxicity assays showed a decrease in the IC₅₀ value of PTX of CU-PTX-LNP (by 5.47-332.7 times in HepG2 and 4.29-143.21 times in SMMC-7221 cells) compared to free PTX. In vivo, CU-PTX-LNP displayed excellent biosafety, significant anti-tumor benefits and enhanced pharmacokinetic behavior with longer mean residence time (MRT_(0-t); CU: 4.31-fold, PTX: 4.61-fold) and half-life (t_1/2z; CU: 1.83-fold, PTX: 2.28-fold) relative to free drugs.

The newly designed CU-PTX-LNP platform may serve as a viable technological support system for the successful production of CU-PTX composite preparations.