Genetic polymorphisms of CYP1A, CYP1B, CYP2C and risk of cervical cancer among rural population of Maharashtra: Findings from a hospital-based case-control study.

BACKGROUND: Last few decades, multiple studies all over the world revealed the association of genetic polymorphism in cytochrome P450 (CYP) genes with risk of developing different type of cancers, but contradictory outcomes were evidenced in case of cervical cancer (CC) risk. Therefore, the discrepancies in earlier reports influenced us to evaluate the association of CYP1A1*2A rs4646903, CYP1B1*3 rs1056836, CYP2C8*2 rs11572103, CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP2C19*2 rs4244285 polymorphisms and CC susceptibility in the women of rural population of Maharashtra. MATERIALS AND METHODS: In this case-control study, genetic association of the polymorphisms in CYP genes was studied by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted among 350 clinically confirmed CC patients and 350 healthy volunteers in a population of south-western Maharashtra. The odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to get the level of association where P ≤ 0.005 was considered as statistically significant. RESULTS: After the analysis of single-nucleotide polymorphism (SNPs) of CYP1A1, CYP1B1, CYP2C8, CYP2C9, and CYP2C19, we noticed that CYP1B1*3 rs1056836 (Leu4326Val) polymorphism possessed a significantly elevated risk (OR = 3.28; 95% CI: 2.18-4.94; P < 0.0001), whereas CYP2C19*2 rs4244285 showed significantly lower risk (OR: 0.53, 95% CI: 0.33-0.85 P < 0.009) of CC in the studied rural population. CONCLUSION: The findings from this study supported that rs1056836 SNP of CYP1B1*3 increase CC development, whereas rs4244285 of CYP2C19*2 lowers the CC risk in the studied population.

Biogenic synthesis of gold nanoparticles using Argemone mexicana L. and their cytotoxic and genotoxic effects on human colon cancer cell line (HCT-15).

BACKGROUND: Nanomedicine has evolved as precision medicine in novel therapeutic approach of cancer management. The present study investigated the efficacy of biogenic gold nanoparticles synthesized using Argemone mexicana L. aqueous extract (AM-AuNPs) against the human colon cancer cell line, HCT-15. RESULTS: Biosynthesis of AM-AuNPs was determined by ultraviolet-visible spectroscopy and further characterized by transmission electron microscopy, X-ray diffraction, and Fourier transition infrared spectroscopy analysis. The cytotoxic activity of AM-AuNPs was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, whereas genotoxicity was evaluated by the DNA fragmentation assay. The expression of apoptosis regulatory genes such as p53 and caspase-3 was explored through semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting to evidence apoptotic cell death in HCT-15 cells. Biogenic AM-AuNPs inhibited cell proliferation in HCT-15 cell line with a half maximal inhibitory concentration (IC50) of 20.53 µg/mL at 24 h and 12.03 µg/mL at 48 h of exposure. The altered cell morphology and increased apoptosis due to AM-AuNPs were also evidenced through nuclear DNA fragmentation and upregulated expression of p53 and caspase-3 in HCT-15 cells. CONCLUSION: The AM-AuNPs may exert antiproliferative and genotoxic effects on HCT-15 cells by cell growth suppression and induction of apoptosis mediated by activation of p53 and caspase-3 genes.