Coleus vettiveroides ethanolic root extract induces cytotoxicity by intrinsic apoptosis in HepG2 cells

• Published in: Journal of applied toxicology Vol. 44; no. 2; pp. 245 - 259
• Main Authors: Mohamed Azar, Kadmad Abdul Hameed, Ezhilarasan, Devaraj, Shree Harini, Karthik
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-02-2024
• Subjects: Actin; anticancer; Anticancer properties; Apoptosis; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Caspase; Cell cycle; Cell proliferation; Coleus; Coleus - metabolism; Cytochrome c; Cytology; Cytoskeleton; Cytotoxicity; Diabetes mellitus; Ethanol; Flow cytometry; G1 phase; Hep G2 Cells; Hepatocellular carcinoma; Humans; Iodides; Leprosy; Leukoderma; Liver cancer; Liver diseases; Liver Neoplasms - metabolism; Mitochondria; Oxidative stress; Propidium iodide; Quercetin; Reactive Oxygen Species - metabolism; Skin diseases; Staining; Toxicity; apoptosis; anticancer; cytotoxicity; hepatocellular carcinoma
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4536

Hepatocellular carcinoma (HCC) contributes to more than 80% of all primary cancers globally and ranks fourth in cancer‐related deaths, due to the lack of an effective, definite therapeutic drug. Coleus vettiveroides (CV) has been used in Indian traditional medicine to treat diabetes, liver ailments, skin diseases, leukoderma, and leprosy. This study investigates the anticancer effect of CV ethanolic root extract in HepG2 cells. HepG2 cells were treated with CV extract, and its cytotoxicity was analyzed by MTT assay. AO/EB staining, propidium iodide staining, DCFH‐DA assay, phalloidine staining, flow cytometry, and qPCR studies were performed for ROS expression, apoptosis and cell cycle analysis. The phytochemical analysis confirmed the presence of quercetin and galangin in CV root extract. The results showed that CV inhibited the proliferation of HepG2 cells, with altered cellular and nuclear morphology. CV was also found to increase intracellular ROS levels and oxidative stress markers in HepG2 cells. CV significantly altered the actin microfilament distribution in HepG2 cells and caused cell cycle arrest at the sub G0‐G1 phase. CV also induced mitochondria‐mediated apoptosis, as evidenced by increased expression of p53, Bax, cytochrome C, Apaf‐1, PARP, caspase‐3 and caspase‐9, and downregulated Bcl‐2 expression. Therefore, CV exerts its anticancer effect by inducing mitochondrial dysfunction, oxidative stress, cytoskeletal disorganization, cell cycle arrest, and mitochondria‐mediated apoptosis, and it could be a potent therapeutic option for HCC.
Hepatocellular carcinoma is one of the leading causes of liver‐related morbidity and mortality. Coleus vettiveroides (CV) is an important ingredient in Indian traditional medicine. Our phytochemical analysis confirmed the presence of quercetin and galangin in the ethanolic root extract of CV. In this study, CV treatment induced dose‐dependent cytotoxicity in HepG2 cells, a hepatocellular cancer cell line. CV treatments induced oxidative stress, apoptosis‐related morphological changes, and cycle arrest at the sub G0‐G1 phase in HepG2 cells.