Colon cancer is one of the most commonly diagnosed malignancies, which begins as a polyp and grows to become cancer. Diosmin (DS) and naringenin (NR) are naturally occurring flavonoids that exhibit various pharmacological activities. Although several studies have illustrated the effectiveness of these flavonoids as anti-cancerous agents individually, the combinatorial impact of these compounds has not been explored. In the present study, the combined effect of DS and NR (DiNar) in colon cancer cell lines HCT116 and SW480 were assessed by targeting apoptosis and inflammatory pathways. The MTT assay was used to evaluate the effect of DiNar on cell proliferation, while Chou-Talalay analysis was employed to determine the combination index of DS and NR. Moreover, flow cytometry was used to monitor cell cycle arrest and population study. The onset of apoptosis was assessed by DAPI staining, DNA fragmentation, and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI). The expression levels of apoptotic pathway markers, Bcl-2, Bax, caspase3, caspase8, caspase9 and p53, and inflammatory markers, NF-κβ, IKK-α and IKK-β, were assessed using western blotting and reverse transcription-quantitative PCR. These results suggested that DiNar treatment acts synergistically and induces cytotoxicity with a concomitant increase in chromatin condensation, DNA fragmentation and cell cycle arrest in the G0/G1 phase. Annexin V-FITC/PI apoptosis assay also showed increased number of cells undergoing apoptosis in the DiNar treatment group. Furthermore, the expression of apoptosis and inflammatory markers was also more effectively regulated under the DiNar treatment. Thereby, these findings demonstrated that DiNar treatment could be a potential novel chemotherapeutic alternative in colon cancer.

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Background Colorectal cancer (CRC) heritability is determined by the composite relations between inherited variants and environmental factors. In developing countries like India CRC incidence rates have been increasing specially. In the present study, we focused on the distribution of FOXO3a gene polymorphisms in North Indian colorectal cancer patients. Methods A case–control study was conducted on 900 samples including 450 colorectal cancer patients and 450 age matched controls. We genotyped the SNPs rs2253310 and rs4946936 via Polymerase Chain Reaction-Restriction fragment length polymorphism (RFLP) analysis and Polymerase Chain Reaction- single stranded conformation polymorphism (SSCP) procedure followed by sequence detection. Results A significantly increased risk of CRC was observed with rs4946936 genotype (P= 0.0393; OR= 1.405 CI=1.051-1.879). GT haplotype although not reaching statistical significance appeared to be at higher “risk” haplotype (OR- 1.164, 95%CI= 0.967~1.401), while as other haplotypes CC (OR- 0.893, 95% CI=0.665~1.200]), CT (OR- 0.806, 95%CI= 0.616~1.055) and GC (OR- 0.994, 95%CI= 0.809~1.221) were found to be “protective” for developing colorectal cancer. Conclusion This study lends support for an increased risk of CRC associated with the rs4946936 polymorphism. Nevertheless, statistically significant association between rs2253310 genotypes and CRC risk was not observed.