Evaluating the effects of flavonoid Apigenin on the apoptosis pathway gene expression on the colon cancer cell line.

Oncogenic mutations which target signal transmission pathways and proteins are frequently observed in colon cancer. Alterations in the signal transmission might cause cell proliferation, removal of control of survival functions and break away from the process known as `apoptosis? or programmed cell death. Apigenin (4?, 5, 7,-trihydroxyflavone), due to its apoptotic, anti-inflammatory, anti-oxidant, anti-metastatic and non-mutagenic properties, is one the leading components which might support targeted treatment options (proapoptotic treatment). Based on this information, the aim of the present study is to evaluate the cytotoxic and apoptotic effects of Apigenin on HT29 cell line.In our study, we explored on the p53 mutant HT29 human colon adenocarcinoma cell line, the cytotoxic and apoptotic effects of Apigenin per se as well as when it was accompanied by 5-Fluorourasil (5-FU) ? a chemotherapeutic agent with high cytotoxicity - on morphological, DNA, RNA (mRNA) and protein levels and for various doses and incubation time.Treatment with Apigenin only for 72h incubation at 90?M dose resulted in the highest apoptotic percentage (24.92%) (p=0.001) while a higher percentage (29.13%) was observed after treatment with the same dose of Apigenin and 5-FU combination for the same incubation duration (p=0.001). These results were confirmed as mRNA and protein expression levels of caspase-3 (effector) and mRNA expression levels of caspase-8 (initiator) increased in comparison to the control groups. On the other hand, mRNA expression levels of mTOR and cyclin D1 which take part in cell proliferation decreased in comparison to the control groups.This is the first study displaying that Apigenin-only treatment results in cell cycle arrest through independent-p53 pathway on the HT29 cell line, activates the caspase cascade and stimulates apoptosis of the HT29 cells. It further shows that use of Apigenin and 5-FU combination leads to a further increase in this effect. In conclusion, our study draws attention to the possible clinical effectiveness of use of Apigenin together with chemotherapeutic agents with high cytotoxicity due to the opportunity to attain suitable apoptotic effect with reduced dose and time in cancer treatment targeting caspase cascade pathway.