The Potential Preventive and Therapeutic Roles of NSAIDs in Prostate Cancer.

Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer.

Lupeol attenuated the NAFLD and PCOS-induced metabolic, oxidative, hormonal, histopathological, and molecular injuries in mice.

Background and purpose: The current study aimed to study the therapeutic effects of lupeol as a nutritional triterpene on non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS) disorders in separate and concurrent models. Experimental approach: This study was performed in three sets and each set contained 4 groups of female mice (n = 6), including control, NAFLD or PCOS and/or NAFLD/PCOS, lupeol, and metformin (MET). The treatment groups following the induction of disorders were treated with lupeol (40 mg/kg, orally) or MET (500 mg/kg, orally) for 28 days. The insulin resistance index and hormonal assessments were conducted on the collected serum samples. Moreover, oxidative stress biomarkers were measured in the liver and ovaries. Histopathological studies and ultimately any changes in the expression of androgen receptors, toll-like receptor (TLR)-2 and TLR-4 were analyzed. Findings/Results: Results revealed that lupeol reduced significantly the insulin resistance index in NAFLD and NAFLD/PCOS-positive animals. Lupeol attenuated remarkably the PCOS and PCOS/NAFLD-elevated concentration of testosterone. lupeol recovered the metabolic disorders-induced oxidative stress and restored the disorders-depleted glutathione. The NAFLD/PCOS-induced hepatic damages such as microvesicular or macrovesicular steatosis and atretic follicles number in the ovary were attenuated in the lupeol-treated mice. Serum level of TNF-α was reduced and the expression of androgen receptors, TLR-4 and TLR-2 were downregulated in the lupeol-treated NAFLD/PCOS-positive animals. Conclusions and implication: The results suggest that lupeol could be a novel nutraceutical for the treatment of metabolic disorders. Lupeol's anti-metabolic disorders effects attribute to its anti-dyslipidemia, antioxidant, and anti-inflammatory properties.

Flavonoids nanostructures promising therapeutic efficiencies in colorectal cancer.

Colorectal cancer is among the frequently diagnosed cancers with high mortality rates around the world. Polyphenolic compounds such as flavonoids are secondary plant metabolites which exhibit anti-cancer activities along with anti-inflammatory effects. However, due to their hydrophobicity, sensitivity to degradation and low bioavailability, therapeutic effects have shown poor therapeutic effect. Nano delivery systems such as nanoliposomes, nanomicelles, silica nanoparticles have been investigated to overcome these difficulties. This review provides a summary of the efficiency of certain flavonoids and polyphenols (apigenin, genistein, resveratrol, quercetin, silymarin, catechins, luteolin, fisetin, gallic acid, rutin, and curcumin) on colorectal cancer models. It comprehensively discusses the influence of nano-formulation of flavonoids on their biological functions, including cellular uptake rate, bioavailability, solubility, and cytotoxicity, as well as their potential for reducing colorectal cancer tumor size under in vivo situations.

Zearalenone and its metabolite exposure directs oestrogen metabolism towards potentially carcinogenic metabolites in human breast cancer MCF-7 cells.

Zearalenone (ZEN) is produced by Fusarium species contaminating various agriculture crops. In this study, the effects of ZEN and its metabolites α-zearalenol (α-ZEL), and ß-zearalenol (ß-ZEL) on the formation of carcinogenic oestrogen-catechols in MCF-7 cells were investigated. To assess the effects of mycoestrogens on the activity of cytochrome P450 1A1 and CYP1B1, the rate of ethoxyresorufin O-deethylation (EROD-assay) was measured. The effects of mycoestrogens on the expression of CYP 1A1, CYP 1B1, aryl-hydrocarbon receptor (AhR), and oestrogen receptor alpha (ERα) were determined by qPCR. The catechol-O-methyltransferase (COMT) activity was measured as the ratio of the methoxy metabolites of oestradiol. Results show that mycoestrogens inhibited significantly the CYP1-dependent EROD activities. In the presence of selective inhibitors, mycoestrogens reduced CYP 1A1 and enhanced CYP 1B1 activity. Quantitative PCR analyses demonstrated the upregulation of AhR and confirmed the selective effect of mycoestrogens on CYP1 expression levels and the decline of the CYP 1A1/CYP 1B1 ratio. Mycoestrogens increased the ratio of 4-MeOE to 2-MeOE2 formation significantly (P < 0.05). Our results suggest that the tested mycoestrogens increase the production of CYP1B1-mediated oestrogen catechol metabolites, directing the biotransformation of E2 towards 4-OHE2, which has been identified earlier as a crucial factor in oestrogen-induced tumour initiation.

Lupeol synergizes with doxorubicin to induce anti-proliferative and apoptotic effects on breast cancer cells.

PURPOSE: Anti-cancer and anti-migration effects of lupeol as a biological pentacyclic triterpenoid were investigated individually and in combination with Doxorubicin (DOX) on MCF-7 and MDA-MB-231 breast cancer cells and human foreskin fibroblasts. METHODS: To uncover the anticancer effect of lupeol and the impact of its combination with DOX, cell viability and scratch assays and dual acridine-orange apoptotic staining were performed. Moreover, the expression of proapoptotic caspase-3 and metastasis-related MMP-9 at the mRNA and protein levels was analyzed using qPCR and western blot techniques. RESULTS: Lupeol synergistically increased the anti-proliferative effect of DOX with IC50 values of 42.55, 62.24 and 65.9 µM on MCF-7, MDA-MB-231 and HFF cells, respectively. Lupeol reduced the cell migration and lowered the DOX-induced cell migration, significantly (p < 0.05). The number of apoptotic cells elevated significantly (p < 0.05) when cancer cells were treated with the combination of lupeol and DOX. Lupeol individually and in combination with DOX up-regulated the expression of caspase-3. The proposed combination therapy synergized (3-4 fold) the down-regulation of MMP-9 expression in MCF-7 and MDA-MB-231 cells. CONCLUSION: Our results indicate that lupeol could be considered as an anticancer agent and anticancer adjuvant in breast cancer-therapy. The anticancer properties of lupeol attribute to its antiproliferative, antimigrative and apoptotic effects.