Zingiberene inhibits in vitro and in vivo human colon cancer cell growth via autophagy induction, suppression of PI3K/AKT/mTOR Pathway and caspase 2 deactivation

Purpose: Colon Cancer (CC) is one of the deadly malignancies and the second most frequent Cancer in the world. The development of drug resistance and dearth of the viable drug options form a serious obstacle in the treatment of CC. Herein, the Anticancer potential of Zingiberene was examined against the CC cells.

Methods: The proliferation rate of the CC cells was assessed by cell counting assay. Autophagy was detected by transmission electron microscopy (TEM). The transfected cells were then treated with varied concentrations of Zingiberene (0, 10, 20 and 40 µM) for 24 h and monitored by fluorescent microscopy. Cell cycle analysis was performed by flow cytometry. Protein expression was determined by immunoblotting.

Results: Zingiberene could considerably inhibit the proliferation of CC cells. The Anticancer activity of Zingiberene against the HT-29 CC cells was found to be due to induction of Autophagy. The Zingiberene triggered Autophagy was also linked with increase in the expression of LC3-II and decrease in p62 expression. However, no apparent effects were observed on the LC3-I expression. Moreover, it was found that zingiberine also caused activation of autophagy-related caspases in the HT-29 cells. Further, it was found that Zingiberene could inhibit the mTOR/PI3K/Akt signalling pathway in the CC cells. Zingiberene also suppressed the weight and volume of the xenografted tumors concentration-dependently.

Conclusions: These results indicate that Zingiberene may inhibit the growth of CC in vitro and in vivo and may be used for the development of systemic therapy against CC.