Artemisia monosperma induces ROS-mediated cell death in human colorectal carcinoma cells via modulating apoptotic genes

Abstract

Background: Colorectal cancer (CRC) is the third most diagnosed cancer in the world. Artemisia monosperma (family: Asteraceae), a flowering plant species in the genus Artemisia, is widely used in traditional medicine. Plant extracts are well documented to combat against cancer diseases. Nevertheless, the outcome of A. monosperma extracts on human colorectal carcinoma cells (HCT-116) have not been investigated in details. Objectives: Thus, herein we aimed to evaluate the cytotoxic effect of different extracts i.e. n-hexane (AM-H), chloroform (AM-C), n-butanol (AM-B), and aqueous (AM-Aq) of A. monosperma against HCT-116 cells and to identify molecular mechanism(s) involved in cytotoxicity. Methods: The HCT-116 cells were treated with 10–1000 μg/mL of extracts for 24 h. Results: Our results displayed that all extracts significantly decreased cell viability in HCT-116 cells and changed the cellular morphology in a dose-dependent way. Among these extracts, AM-C showed higher cytotoxic activity with IC50 of 250.5 μg/mL. Further AM-C extract increased ROS production and reduced MMP level in HCT-116 cells. Moreover, AM-C extract induces cell apoptosis by the upregulation of proapoptotic related genes (p53, Bax, caspase-3, and caspase-9) and downregulation of antiapoptotic gene, Bcl-2. More significantly, these results revealed that AM-C extract enhances apoptosis in HCT-116 cells associated with ROS generation and mitochondrial dysfunction. Conclusion: Our findings suggest that the extracts of A. monosperma can be an auspicious therapeutic agent against colorectal cancer.

Keywords

• HCT-116 cells
• Artemisia monosperma
• Cytotoxicity
• ROS
• MMP
• Apoptosis