• cancer prevention
• natural products
• phytotherapy
• signalling pathways

• Humans
• Mouth Neoplasms/prevention & control
• Asia, Southeastern
• Phytochemicals/therapeutic use
• Biological Products/therapeutic use
• Phytotherapy
• Diet
• Plants, Medicinal

• Compound taxus
• G2/M arrest
• Hepatocellular carcinoma
• NF-κB signaling pathway
• Radiosensitivity

• cancer treatment
• curcumin
• radiation therapy
• radioprotection
• radiosensitization

• Curcumin/pharmacology
• Curcumin/therapeutic use
• Antineoplastic Agents/pharmacology
• Radiation-Sensitizing Agents/pharmacology
• Radiation-Sensitizing Agents/therapeutic use

• Natural products
• Oral cancer
• Squamous cell carcinoma (SCC)
• Tumor microenvironment (TME)

• Humans
• Tumor Microenvironment
• Neoplasms
• Mouth Neoplasms/drug therapy
• Nanoparticles

• colorectal cancer
• ginsenoside Rh2
• immunomodulation
• radiotherapy

• CSH-2020-C-024 Chung Shan Medical University Hospital, Taichung, Taiwan.

• nuclear factor-κB (NF-κB)
• pathological angiogenesis
• therapy
• tumourigenesis

• Humans
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Signal Transduction
• I-kappa B Proteins/metabolism
• Neoplasms/drug therapy
• Neoplasms/etiology
• Neovascularization, Pathologic/metabolism
• Apoptosis

The global incidence of oral cancer has steadily increased in recent years and is associated with high morbidity and mortality. Oral cancer is the most common cancer in the head and neck region, and is predominantly of epithelial origin (i.e. squamous cell carcinoma). Oral cancer treatment modalities mainly include surgery with or without radiotherapy and chemotherapy. Though proven effective, chemotherapy has significant adverse effects with possibilities of tumor resistance to anticancer drugs and recurrence. Thus, there is an imperative need to identify suitable anticancer therapies that are highly precise with minimal side effects and to make oral cancer treatment effective and safer. Among the available adjuvant therapies is curcumin, a plant polyphenol isolated from the rhizome of the turmeric plant Curcuma longa. Curcumin has been demonstrated to have anti-infectious, antioxidant, anti-inflammatory, and anticarcinogenic properties. Curcumin has poor bioavailability, which has been overcome by its various analogues and nanoformulations, such as nanoparticles, liposome complexes, micelles, and phospholipid complexes. Studies have shown that the anticancer effects of curcumin are mediated by its action on multiple molecular targets, including activator protein 1, protein kinase B (Akt), nuclear factor κ-light-chain-enhancer of activated B cells, mitogen-activated protein kinase, epidermal growth factor receptor (EGFR) expression, and EGFR downstream signaling pathways. These targets play important roles in oral cancer pathogenesis, thereby making curcumin a promising adjuvant treatment modality. This review aims to summarize the different novel formulations of curcumin and their role in the treatment of oral cancer.

• Oral cancer
• Oral squamous cell carcinoma
• Analogues
• Curcumin
• Adjuvant therapy
• Nanocurcumin
• Curcumin nanoformulations
• Curcumin analogues

• cancer stem cells
• lncRNA HOXA11-AS
• miR-518a-3p
• oral squamous cell carcinoma
• radiosensitivity

• Humans
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/radiotherapy
• Carcinoma, Squamous Cell/metabolism
• Squamous Cell Carcinoma of Head and Neck/genetics
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Cell Line, Tumor
• Mouth Neoplasms/genetics
• Mouth Neoplasms/radiotherapy
• Mouth Neoplasms/metabolism
• Transcription Factors/genetics
• Neoplastic Stem Cells/pathology
• Head and Neck Neoplasms/genetics
• Head and Neck Neoplasms/radiotherapy
• Head and Neck Neoplasms/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Homeodomain Proteins/genetics

• JJMS2021-20 General Project of Haiyan Scientific Research Fundation

Radioresistance inducing by hypoxic microenvironment of hepatocellular carcinoma is a major obstacle to clinical radiotherapy. Advanced nanomedicine provides an alternative to alleviate the hypoxia extent of solid tumor, even to achieve effective synergistic treatment when combined with chemotherapy or radiotherapy.

Herein, we developed a self-assembled nanoparticle based on hemoglobin and curcumin for photoacoustic imaging and radiotherapy of hypoxic hepatocellular carcinoma. The fabricated nanoparticles inhibited hepatoma migration and vascular mimics, and enhanced the radiosensitivity of hypoxic hepatoma cells in vitro via repressing cell proliferation and DNA damage repair, as well as inducing apoptosis. Benefit from oxygen-carrying hemoglobin combined with polyphenolic curcumin, the nanoparticles also effectively enhanced the photoacoustic contrast and the efficacy of radiotherapy for hepatocellular carcinoma in vivo.

Together, the current study offered a radiosensitization platform for optimizing the efficacy of nanomedicines on hypoxic radioresistant tumor.

The online version contains supplementary material available at 10.1186/s12951-022-01316-w.

Currently, radiation therapy is one of the standard therapies for cancer treatment. Since the first applications, the field of radiotherapy has constantly improved, both in imaging technologies and from a dose-painting point of view. Despite this, the mechanisms of resistance are still a great problem to overcome. Therefore, a more detailed understanding of these molecular mechanisms will allow researchers to develop new therapeutic strategies to eradicate cancer effectively. This review focuses on different transcription factors activated in response to radiotherapy and, unfortunately, involved in cancer cells’ survival. In particular, ionizing radiations trigger the activation of the immune modulators STAT3 and NF-κB, which contribute to the development of radiation resistance through the up-regulation of anti-apoptotic genes, the promotion of proliferation, the alteration of the cell cycle, and the induction of genes responsible for the Epithelial to Mesenchymal Transition (EMT). Moreover, the ROS-dependent damaging effects of radiation therapy are hampered by the induction of antioxidant enzymes by NF-κB, NRF2, and HIF-1. This protective process results in a reduced effectiveness of the treatment, whose mechanism of action relies mainly on the generation of free oxygen radicals. Furthermore, the previously mentioned transcription factors are also involved in the maintenance of stemness in Cancer Stem Cells (CSCs), a subset of tumor cells that are intrinsically resistant to anti-cancer therapies. Therefore, combining standard treatments with new therapeutic strategies targeted against these transcription factors may be a promising opportunity to avoid resistance and thus tumor relapse.

• ROS - reactive oxygen species
• cancer stem cells
• inflammation
• radiation resistance
• radiotherapy
• transcription factors

Androgen deprivation therapy (ADT) is one of the typical treatments used for patients with prostate cancer (PCa). ADT, however, may fail when PCa develops castration-resistance. Fatty acid synthase (FASN), a critical enzyme involved in fatty acid synthesis, is found to be up-regulated in PCa. Since enzalutamide and ADT are frequently used for the treatment of PCa, the present study aimed to unravel the underlying mechanism of combination of orlistat, an FASN inhibitor, and enzalutamide using PC3 cell line; and orlistat and castration in PC3 tumor-bearing animal model. Cytotoxicity was determined by AlamarBlue assay. Drug effects on the cell cycle and protein expressions were assayed by the flow cytometry and Western blot. Electromobility shift assay was used to evaluate the NF-κB activity. The tumor growth delay, expressions of the signaling-related proteins, and histopathology post treatments of orlistat and castration were evaluated in PC3 tumor-bearing mouse model. The results showed that orlistat arrested the PC3 cells at the G₁ phase of the cell cycle and enhanced the cytotoxic effects of enzalutamide synergistically. Pretreatment with orlistat combined with castration inhibited the tumor growth significantly compared with those of castration and orlistat treatments alone in PC3 tumor-bearing mice. Combination treatment reduced both FASN and NF-κB activities and their downstream effector proteins. The present study demonstrated the synergistic effects of orlistat combined with enzalutamide in vitro and castration in vivo on human PCa.

• NF-kB
• castration therapy
• enzalutamide
• fatty acid synthase
• orlistat
• prostate cancer

• curcumin
• nuclear factor-κB
• oral squamous cell carcinoma
• p65
• specificity protein 1

• Animals
• Antineoplastic Agents/pharmacology
• Curcumin/pharmacology
• Disease Models, Animal
• Humans
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Neoplasms/pathology
• Neoplasms/radiotherapy
• Radiation-Sensitizing Agents/pharmacology
• Signal Transduction

• Calebin-A
• Histone acetyltransferase
• MPNST
• NF1
• Survivin
• hTERT

• Animals
• Antineoplastic Agents, Phytogenic/pharmacology
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cinnamates/pharmacology
• Enzyme Activation/drug effects
• Histone Acetyltransferases/metabolism
• Histone Deacetylases/metabolism
• Humans
• Male
• Mice, Inbred BALB C
• Monoterpenes/pharmacology
• Nerve Sheath Neoplasms/drug therapy
• Nerve Sheath Neoplasms/enzymology
• Nerve Sheath Neoplasms/pathology
• Neurofibroma, Plexiform/pathology
• Neurofibromatosis 1/pathology
• Phosphorylation/drug effects
• Signal Transduction/drug effects
• Survivin/genetics
• Survivin/metabolism
• Telomerase/genetics
• Telomerase/metabolism
• Xenograft Model Antitumor Assays

The aim of the present study was to verify the effects of fluoxetine on dysregulation of apoptosis and invasive potential in human hepatocellular carcinoma (HCC) SK-Hep1 and Hep3B cells. Cells were treated with different concentrations of fluoxetine for different times. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used for testing the effects of fluoxetine on cell viability. The regulation of apoptosis signaling, and anti-apoptotic, proliferation, and metastasis-associated proteins after fluoxetine treatment were assayed by flow cytometry and Western blotting assay. The detection of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation after fluoxetine treatment was performed by NF-κB reporter gene assay. The results demonstrated that fluoxetine significantly reduced cell viability, cell migration/invasion, NF-κB, extracellular signal-regulated kinases (ERK) activation, and expression of anti-apoptotic (Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (C-FLIP), Myeloid cell leukemia-1 (MCL-1), X-Linked inhibitor of apoptosis protein (XAIP), and Survivin), proliferation (Cyclin-D1), angiogenesis (vascular endothelial growth factor (VEGF)), and metastasis-associated proteins (matrix metalloproteinase-9 (MMP-9)). Fluoxetine also significantly induced apoptosis, unregulated extrinsic (activation of first apoptosis signal protein and ligand (Fas/FasL), and caspase-8) and intrinsic (loss of mitochondrial membrane potential (ΔΨm) pathways and increased Bcl-2 homologous antagonist killer (BAK) apoptosis signaling. Taken together, these results demonstrated that fluoxetine induced apoptosis through extrinsic/intrinsic pathways and diminished ERK/NF-κB-modulated anti-apoptotic and invasive potential in HCC cells in vitro.

• NF-κB
• apoptosis
• fluoxetine
• human hepatocellular carcinoma

• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Apoptosis/genetics
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Extracellular Signal-Regulated MAP Kinases/metabolism
• Fluoxetine/pharmacology
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Models, Biological
• NF-kappa B/metabolism
• Signal Transduction/drug effects

• cancer
• chemotherapy
• curcumin
• inflammation
• radiotherapy

• 6-MITC
• I7447
• I7557
• apoptosis
• mitosis
• oral cancer
• wasabi

• Antineoplastic Agents/chemical synthesis
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Cell Cycle Checkpoints/drug effects
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Checkpoint Kinase 1/metabolism
• Down-Regulation
• Gene Expression Regulation, Neoplastic/drug effects
• Histones/metabolism
• Humans
• Isothiocyanates/chemical synthesis
• Isothiocyanates/chemistry
• Isothiocyanates/pharmacology
• Mouth Neoplasms/drug therapy
• Mouth Neoplasms/metabolism
• Oxygen/chemistry
• Phosphorylation
• Plant Extracts/chemistry
• Wasabia/chemistry
• cdc25 Phosphatases/metabolism

• MMH-E-107-13 Mackay Memorial Hospital
• MOST 106-2314-B-195-002-MY3 Ministry of Science and Technology, Taiwan

• 4- Shogaol (PubChem CID: 9794897)
• 6- Shogaol (PubChem CID: 5281794)
• Apigenin (PubChem CID: 5280443)
• Berberine (PubChem CID: 2353)
• Bergamottin (PubChem CID: 5471349)
• Caffeic acid (PubChem CID: 689043)Capsaicin (PubChem CID: 1548943)
• Cancer
• Cardamonin (PubChem CID: 641785)
• Casticin(PubChem CID: 5315263)
• Chrysin (PubChem CID: 5281607)
• Cryptotanshinone (PubChem CID: 160254)
• Cucurbitacin (PubChem CID: 5281319)
• Curcumin (PubChem CID: 969516)
• EGCG (PubChem CID: 65064)
• Ellagic acid (PubChem CID: 5281855)
• Escin (PubChem CID: 16211024)
• Fistein (PubChem CID: 5281614)
• Gambogic acid (PubChem CID: 16072310)
• Gingerol (PubChem CID: ‎442793)
• Gossypin (PubChem CID: 5281621)
• Honokiol (PubChem CID: 72303)
• Inflammation
• Luteolin (PubChem CID: 5280445)
• Mangiferin (PubChem CID: 5281647)
• Metastasis
• Natural compounds
• Piperlongumine (PubChem CID: 637858)
• Polyphenols
• Pterostilbene (PubChem CID: 5281727)
• Quercetin (PubChem CID: 5280343)
• Resveratrol (PubChem CID: 445154)
• Rutin (PubChem CID: 5280805)
• Sesamin (PubChem CID: 72307)
• Transcription factors
• Ursolic acid (PubChem CID: 64945)
• Wogonin (PubChem CID: 5281703)
• Xanthohumol (PubChem CID: 639665)

• anti-angiogenesis
• anti-metastasis
• nuclear factor-κB
• regorafenib

Curcumin is widely reported to have remarkable medicinal - and antineoplastic - properties. This review details curcumin’s relationship with radiotherapy (RT), principally as a radiosensitizer for various malignancies and a radioprotector for normal tissues. First, examples of radiosensitization are provided for various cancers: Pediatric, lymphoma, sarcoma, prostate, gynecologic, pancreas, liver, colorectal, breast, lung, head/neck, and glioma. It is not the purpose of this article to comprehensively review all radiosensitization data; however, high-quality studies are discussed in relationship to currently-controversial RT questions for many cancers, and thus the importance of developing a natural radiosensitizer. Attention is then shifted to radioprotection, for which supporting research is discussed for the following RT toxicities: Dermatitis, pneumonitis, cataractogenesis, neurocognition, myelosuppression, secondary malignancies, and mucositis/enteritis. Though there is fewer data for radioprotection, the overall quality of clinical evidence is higher, and small clinical trials implicating the efficacy of curcumin for RT toxicities (vs placebo/current therapies) are also detailed. Though the overall level of evidence for curcumin as a radiosensitizer and radioprotector is low, it must be recognized that risks of adverse effects are exceedingly low, and clinicians may need to judge the yet-unproven rewards with low toxicity risks.

• Curcumin
• Turmeric
• Radiation therapy
• Cancer
• Radioprotection
• Radiosensitization

• Bufalin
• MAPKs
• MMPs
• NCI-H460 Cells
• NF-κB

Oral squamous cell carcinoma often causes bone invasion resulting in poor prognosis and affects the quality of life for patients. Herein, we combined radiation with sorafenib, to evaluate the combination effect on tumor progression and bone erosion in an in situ human OSCC-bearing mouse model. Treatment procedure were arranged as following groups: (a) normal (no tumor); (b) control (with tumor); (c) sorafenib (10 mg/kg/day); (d) radiation (single dose of 6 Gy); (e) pretreatment (sorafenib treatment for 3 days prior to radiation), and (f) concurrent treatment (sorafenib and radiation on the same day). The inhibition of tumor growth and expression level of p65 of NF-κB in tumor tissues were the most significant in the pretreatment group. EMSA and Western blot showed that DNA/NF-κB activity and the expressions of NF-κB-associated proteins were down-regulated. Notably, little to no damage in mandibles and zygomas of mice treated with combination of sorafenib and radiation was found by micro-CT imaging. In conclusion, sorafenib combined with radiation suppresses radiation-induced NF-κB activity and its downstream proteins, which contribute to radioresistance and tumorigenesis. Additionally, bone destruction is also diminished, suggesting that combination treatment could be a potential strategy against human OSCC.

The effects and possible underlying mechanism of curcumin combined with radiation in human hepatocellular carcinoma (HCC) cells in vitro were evaluated. The effects of curcumin, radiation, and combination of both on cell viability, apoptosis, NF-κB activation, and expressions of NF-κB downstream effector proteins were investigated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), NF-κB reporter gene, mitochondrial membrane potential (MMP), electrophoretic mobility shift (EMSA), and Western blot assays in Huh7-NF-κB-luc2, Hep3B, and HepG2 cells. Effect of I kappa B alpha mutant (IκBαM) vector, a specific inhibitor of NF-κB activation, on radiation-induced loss of MMP was also evaluated. Results show that curcumin not only significantly enhances radiation-induced cytotoxicity and depletion of MMP but inhibits radiation-induced NF-κB activity and expressions of NF-κB downstream proteins in HCC cells. IκBαM vector also shows similar effects. In conclusion, we suggest that curcumin augments anticancer effects of radiation via the suppression of NF-κB activation.