Anticancer activity of safranal against colon carcinoma is due to induction of apoptosis and G2/M cell cycle arrest mediated by suppression of mTOR/PI3K/Akt pathway.

PURPOSE

Colon cancer is among the deadliest malignancies and is responsible for a significant number of deaths across the globe. The treatment options for colon cancer are limited and with lot of side effects. In this study we evaluated the potential anticancer effects of safranal against colo-205 colon cancer cells along with evaluation of its effects on apoptosis, cell cycle phase distribution, reactive oxygene species (ROS) and PI3K/AKT/m-TOR signalling pathway.

METHODS

Cell viability was examined by MTT assay. Apoptosis was checked by DAPI staining, comet assay and annexin V/propidium iodide (PI) staining involving the use of fluorescence microscopy and flow cytometry. ROS, mitochondrial membrane potential (MMP) and cell cycle phase distribution were checked by flow cytometry using different fluorescent probes. Effects of safranal on the protein expression of PI3K/AKT/m-TOR were studied by western blot assay.

RESULTS

The results revealed that safranal suppressed the proliferation of colo-205 cancer cells with an IC50 of 20 μM. Furthermore, the anticancer effects of safranal were found to be due to accretion of ROS and decrease in the MMP, ultimately leading to apoptosis of colo-205 cancer cells. In addition, safranal caused increase in the expression of Bax in parallel with concomitant reduction in the expression of Bcl-2. Safranal also triggered G2/M cell cycle arrest and inhibition of PI3K/AKT/mTOR signalling pathway.

CONCLUSION

In conclusion, the above results indicate that safranal could prove a potential lead molecule in the treatment of colon cancer, provided further in vivo studies are carried out.