• Dyslipidemia
• Lipid regulating agents
• Metastasis
• Statins
• Tumor

• Humans
• Hypolipidemic Agents/pharmacology
• Hypolipidemic Agents/therapeutic use
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Dyslipidemias/drug therapy
• Neoplasms/drug therapy
• Neoplasms/complications
• Lipids

• Liver cancer
• hydrophilic statins
• incidence
• lipophilic statins
• meta-analysis
• statin

• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Incidence
• Simvastatin
• Lovastatin
• Liver Neoplasms/epidemiology
• Liver Neoplasms/prevention & control

• Abiraterone acetate
• Metastatic castration-resistant prostate cancer
• Metformin
• Statins

• FOXC1
• chemokine
• cholesterol
• lung fibroblasts
• lung metastasis
• triple-negative breast cancer

The importance of statins in cancer has been discussed in many studies. They are known for their anticancer properties against solid tumors of the liver or lung, as well as diffuse cancers, such as multiple myeloma or leukemia. Currently, the most commonly used statins are simvastatin, rosuvastatin and atorvastatin. The anti-tumor activity of statins is largely related to their ability to induce apoptosis by targeting cancer cells with high selectivity. Statins are also involved in the regulation of the histone acetylation level, the disturbance of which can lead to abnormal activity of genes involved in the regulation of proliferation, differentiation and apoptosis. As a result, tumor growth and its invasion may be promoted, which is associated with a poor prognosis. High levels of histone deacetylases are observed in many cancers; therefore, one of the therapeutic strategies is to use their inhibitors. Combining statins with histone deacetylase inhibitors can induce a synergistic anticancer effect.

• anticancer therapy
• cancer
• cancer prevention
• statins

• Active surveillance
• Diet
• Metformin
• Prostate cancer
• Statins

• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Male
• Metformin/therapeutic use
• Prostatic Neoplasms/diet therapy
• Prostatic Neoplasms/therapy
• Secondary Prevention
• Watchful Waiting

Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014–2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88–0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13–1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.

• case-control study
• detection bias
• direct anticoagulant agents
• prostate cancer
• warfarin

• biochemical relapse
• concomitant medications
• localised prostate cancer
• metformin
• radiotherapy
• α1 receptor blockers

• Selective estrogen receptor modulators
• cancer
• cell proliferation
• cholesterol metabolism
• intracellular cholesterol trafficking

Statins, which are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, reduce cholesterol blood levels and the risk of developing cardiovascular diseases and their related complications. In addition to this main activity, statins show pleiotropic effects such as antioxidant, anti-inflammatory and antiproliferative properties, with applications in many pathologies. Based on their antiproliferative properties, in vitro and in vivo studies have investigated their effects on various types of cancer (i.e., breast cancer, prostate cancer, colorectal cancer, ovarian cancer, lung cancer) with different genetic and molecular characteristics. Many positive results were obtained, but they were highly dependent on the physiochemical properties of the statins, their dose and treatment period. Combined therapies of statins and cytotoxic drugs have also been tested, and synergistic or additive effects were observed. Moreover, observational studies performed on patients who used statins for different pathologies, revealed that statins reduced the risk of developing various cancers, and improved the outcomes for cancer patients. Currently, there are many ongoing clinical trials aimed at exploring the potential of statins to lower the mortality and the disease-recurrence risk. All these results are the foundation of new treatment directions in cancer therapy.

• Statins
• Cancer
• Pleiotropic effects
• Risk reduction
• Clinical trials
• 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase
• Mevalonate pathway

• Anti-inflammatory
• Antibiotic
• Antidiabetic
• Antifungal
• Antipsychotic
• Aspirin
• Cancer
• Drug repurposing/repositioning
• Metformin
• PDE inhibitors

• #PCSM
• #ProstateCancer
• 5α-reductase inhibitors/therapeutic use
• Body mass index
• Middle aged
• Obesity
• Prostate

• 8-hydroxy-2′-deoxyguanosine levels
• DNA damage
• Dyslipidemia
• cytokinesis-block micronucleus cytome assay
• micronucleus
• statin therapy

Prostate cancer is the most common type of cancer and the leading cause of cancer deaths among men in many countries. Preventing progression is a major concern for prostate cancer patients on active surveillance, patients with recurrence after radical therapies, and patients who acquired resistance to systemic therapies. Inflammation, which is induced by various factors such as infection, microbiome, obesity, and a high-fat diet, is the major etiology in the development of prostate cancer. Inflammatory cells play important roles in tumor progression. Various immune cells including tumor-associated neutrophils, tumor-infiltrating macrophages, myeloid-derived suppressor cells, and mast cells promote prostate cancer via various intercellular signaling. Further basic studies examining the relationship between the inflammatory process and prostate cancer progression are warranted. Interventions by medications and diets to control systemic and/or local inflammation might be effective therapies for prostate cancer progression. Epidemiological investigations and basic research using human immune cells or mouse models have revealed that non-steroidal anti-inflammatory drugs, metformin, statins, soy isoflavones, and other diets are potential interventions for preventing progression of prostate cancer by suppressing inflammation. It is essential to evaluate appropriate indications and doses of each drug and diet.

• NSAIDs
• cytokine
• immune cell
• inflammation
• intervention
• metformin
• mouse model
• prostate cancer
• statin

• atorvastatin
• doxycycline
• glioblastoma
• mebendazole
• metabolic targeting
• metformin
• off-label
• pluralistic evidence

Although recent evidence has suggested that a high-fat diet (HFD) plays an important role in prostate carcinogenesis, the underlying mechanisms have largely remained unknown. This review thus summarizes previous preclinical studies that have used prostate cancer cells and animal models to assess the impact of dietary fat on prostate cancer development and progression. Large variations in the previous studies were found during the selection of preclinical models and types of dietary intervention. Subcutaneous human prostate cancer cell xenografts, such as LNCaP, LAPC-4, and PC-3 and genetic engineered mouse models, such as TRAMP and Pten knockout, were frequently used. The dietary interventions had not been standardized, and distinct variations in the phenotype were observed in different studies using distinct HFD components. The use of different dietary components in the research models is reported to influence the effect of diet-induced metabolic disorders. The proposed underlying mechanisms for HFD-induced prostate cancer were divided into (1) growth factor signaling, (2) lipid metabolism, (3) inflammation, (4) hormonal modulation, and others. A number of preclinical studies proposed that dietary fat and/or obesity enhanced prostate cancer development and progression. However, the relationship still remains controversial, and care should be taken when interpreting the results in a human context. Future studies using more sophisticated preclinical models are imperative in order to explore deeper understanding regarding the impact of dietary fat on the development and progression of prostate cancer.

• animal model
• diet
• fat
• in vitro
• in vivo
• mouse
• prostate cancer

• Breast cancer
• Lipophilicity
• Metastasis
• Prenylation
• Secondary prevention
• Statins

• Antineoplastic Combined Chemotherapy Protocols/pharmacology
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Breast Neoplasms/drug therapy
• Breast Neoplasms/mortality
• Breast Neoplasms/prevention & control
• Cardiovascular Diseases/drug therapy
• Cardiovascular Diseases/epidemiology
• Clinical Trials as Topic
• Comorbidity
• Disease Progression
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Incidence
• Neoplasm Recurrence, Local/epidemiology
• Neoplasm Recurrence, Local/prevention & control
• Treatment Outcome

• I01 BX003368 BLRD VA
• UH3 TR000496 NCATS NIH HHS
• CA199947 NCI NIH HHS
• F30 CA199947 NCI NIH HHS
• UH2 TR000496 NCATS NIH HHS
• U.S. Department of Veterans Affairs
• National Center for Advancing Translational Sciences
• National Cancer Institute

• Apoptosis
• Cytotoxicity
• Flavonoids
• HMG-CoA reductase
• Multidrug resistance
• P-glycoprotein
• Statins

• ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Cell Line, Tumor
• Cell Membrane/drug effects
• Cell Membrane/metabolism
• Cell Proliferation/drug effects
• Cholesterol/blood
• Colonic Neoplasms/blood
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/metabolism
• Drug Resistance, Multiple/drug effects
• Drug Resistance, Neoplasm/drug effects
• Drug Therapy, Combination/methods
• Flavonoids/pharmacology
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology

• cholesterol
• prostate cancer
• statins

• Cholesterol
• Fatty acid
• Metabolism
• Prostate cancer

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in the western world, and the mortality rate from PCa in Asia has been increasing recently. Statins are potent inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and are commonly used for treating hyperlipidemia, with beneficial effects for cardiovascular disease and they also exhibit anti-cancer activity. However, the protective effects of statins against PCa are controversial. In this study, we investigated the effect of two types of statins (simvastatin and lovastatin) and the mortality rate of PCa patients by using the Taiwan National Health Insurance Research Database (NHIRD). A total of 15,264 PCa patients with hyperlipidemia records and medical claims from the Registry of Catastrophic Illness were enrolled. The patients were divided into two cohorts based on their statin use before the diagnosis of PCa: statin users (n = 1,827) and non-statin users (n = 1,826). The results showed that patients who used statins exhibited a significantly reduced risk of mortality from PCa [adjusted hazard ratio (HR) = 0.84, 95% CI = 0.73–0.97]. Analysis of the cumulative defined daily dose (DDD) indicated that patients who were prescribed simvastatin ≥ 180 DDD had a dramatically decreased risk of death from PCa (adjusted HR = 0.63; 95% CI = 0.51–0.77). This population-based cohort study demonstrated that statin use significantly decreased the mortality of PCa patients, and that this risk was inversely associated with the cumulative DDD of simvastatin therapy. The results of this study revealed that statins may be used for drug repositioning and in the development of a feasible approach to prevent death from PCa.

• HMG-CoA reductase
• cohort study
• hyperlipidemia
• prostate cancer
• statin

Prostate cancer is one of the most common malignant tumors around the world. Hyperlipidemia is considered as one of the most important risk factors for the development of prostate cancer. Simvastatin is widely used for the treatment of hyperlipidemia and was previously shown to induce apoptosis in several cancer types including lung, colon, pancreas, breast, and prostate cancer. In this study we aimed to explore the potential role of simvastatin in enhancing irinotecan-induced apoptosis in prostate cancer cells. In addition, the underlying molecular mechanisms driving this potential effect of simvastatin were also explored. PC3 cells were treated with simvastatin, irinotecan or combination. Cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetric assay. Flow cytometry technique was used to analyze apoptosis and cell cycle progression. Western blot was used for detection of protein expression. Results showed that simvastatin has a significant anti-proliferative activity on PC3 cells. Combined treatment of simvastatin with irinotecan exhibited a significant inhibition of PC3 cell growth compared to each treatment alone. Flow cytometry analysis showed that PC3 cell treatment with simvastatin and irinotecan combination demonstrated a remarkable increase in the percentage of apoptotic cells and those accumulated at G0/G1 phase when compared to each treatment alone. Moreover, induction of apoptosis was caspase-independent. Western blot showed that apoptosis was accompanied by upregulation of GRP-78 level and downregulation of Mcl-1 levels in a time-dependent manner. The results of this study demonstrated that combined treatment of simvastatin with chemotherapeutic agents such as irinotecan resulted in enhancement of growth inhibition and induction of prostate cancer cell apoptosis.

• Apoptosis
• Irinotecan
• Prostate cancer
• Simvastatin