Anticancer activity of Ashwagandha against human head and neck cancer cell lines

• Published in: Journal of oral pathology & medicine Vol. 45; no. 3; pp. 193 - 201
• Main Authors: Lee, Haeng-Eun, Shin, Ji-Ae, Jeong, Joseph H., Jeon, Jae-Gyu, Lee, Min-Ho, Cho, Sung-Dae
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.03.2016
• Subjects: Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Ashwagandha; Bcl-2-Like Protein 11 - deficiency; Bcl-2-Like Protein 11 - genetics; Bcl-2-Like Protein 11 - metabolism; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Caspase 8 - metabolism; Caspase 9 - drug effects; Caspase 9 - metabolism; Cell Line, Tumor; Cytochromes c - metabolism; Dentistry; Enzyme Activation - drug effects; head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondrial Membranes - drug effects; Mouth Neoplasms - drug therapy; Plant Extracts - pharmacology; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Squamous Cell Carcinoma of Head and Neck; Up-Regulation; Withanolides - pharmacology; head and neck cancer; apoptosis; Ashwagandha
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.12353

Background The aim of this study was to determine the apoptotic activity of methanol extract of Ashwagandha (MEAG) and in human head and neck squamous cell carcinoma (HNSCC) cells and to investigate the underlying mechanisms. Methods We investigated the effects of MEAG on programmed cell death in HNSCC cells using a Live/Dead assay, detection of nuclear morphologic changes, Mitotracker, siRNA knockdown, and RT‐PCR. Results Treatment with MEAG showed dose‐dependent growth‐inhibitory activity that attribute to caspase‐dependent apoptosis. Loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase 9 suggested that MEAG leads to activation of mitochondria‐mediated apoptosis. MEAG selectively upregulated the expression of Bim protein at the transcriptional level and induced the translocation of Bim into the mitochondria. Knockdown of Bim by siRNA partially blocked MEAG‐mediated apoptosis. MEAG also caused an increase in truncated Bid (t‐Bid), cleaved caspase‐8, and death receptor 5 (DR5). Interestingly, withaferin A (WA), a bioactive component of MEAG, clearly induced apoptosis accompanied by upregulation of Bim, t‐Bid, caspase‐8, and DR5 similar to the effects of MEAG. Conclusions These suggest that MEAG and WA may be potential natural materials for the treatment of HNSCC.