Induction of G0/G1 phase cell cycle arrest and apoptosis by thymol through ROS generation and caspase-9/-3 activation in breast and colorectal cancer cell lines

Abstract

ABSTRACT Background: Cancer is a major malignancy and one of the leading causes of death; it calls for a proactive strategy for the cure. Herbs are reservoirs of novel chemical entities and their phytochemical exploration has contributed considerably to the discovery of new anticancer drugs. Thymol, a natural phenolic monoterpenoid, has been implicated with many medicinal properties, including anticancer ones. However, the anti-proliferative and apoptosis-inducing ability of thymol on MDA-MB-231 and HCT-8 cell lines has not been studied yet in detail, and hence this study was conceived. Materials and Methods: We studied the cytotoxicity, morphological alterations of the cell, oxidative stress, cell cycle modulation, apoptosis and expression of apoptosis-related proteins that ensued due to thymol treatment in these cancer cells. Results: Thymol inhibited the cell proliferation, altered the morphology of the cells, increased the intracellular ROS level, arrested the cells in G0/G1 phase, induced apoptosis, upregulated pro-apoptotic protein p53 expression, downregulated anti-apoptotic protein Bcl-xL expression, and activated caspase-9 and -3. Conclusion: These findings elucidate that thymol induces apoptosis through the intrinsic pathway, in MDA-MB-231 breast and HCT-8 colorectal cancer cells through ROS generation and G0/G1 phase cell cycle arrest. This reiterates the broad-spectrum anti-tumor potential of thymol and provides an insight to study further to be developed into an anticancer drug.