PMID- 26332363 OWN - NLM STAT- MEDLINE DCOM- 20170123 LR - 20190221 IS - 1600-0714 (Electronic) IS - 0904-2512 (Linking) VI - 45 IP - 3 DP - 2016 Mar TI - Anticancer activity of Ashwagandha against human head and neck cancer cell lines. PG - 193-201 LID - 10.1111/jop.12353 [doi] AB - 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. CI - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Lee, Haeng-Eun AU - Lee HE AD - Department of Oral Pathology, School of Dentistry and Institute of Biodegradable Material, Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, Jeon-ju, Korea. FAU - Shin, Ji-Ae AU - Shin JA AD - Department of Oral Pathology, School of Dentistry and Institute of Biodegradable Material, Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, Jeon-ju, Korea. FAU - Jeong, Joseph H AU - Jeong JH AD - Department of Dermatology and Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA. FAU - Jeon, Jae-Gyu AU - Jeon JG AD - Department of Preventive Dentistry, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea. FAU - Lee, Min-Ho AU - Lee MH AD - Department of Dental Biomaterials and Institute of Biodegradable Material, Institute of Oral Bioscience and BK21 Plus Project, School of Dentistry, Chonbuk National University, Jeonju, Korea. FAU - Cho, Sung-Dae AU - Cho SD AD - Department of Oral Pathology, School of Dentistry and Institute of Biodegradable Material, Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, Jeon-ju, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150831 PL - Denmark TA - J Oral Pathol Med JT - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology JID - 8911934 RN - 0 (Antineoplastic Agents) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Bcl-2-Like Protein 11) RN - 0 (Plant Extracts) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFRSF10B protein, human) RN - 0 (Withanolides) RN - 9007-43-6 (Cytochromes c) RN - EC 3.4.22.- (Caspase 8) RN - EC 3.4.22.- (Caspase 9) RN - L6DO3QW4K5 (withaferin A) RN - V038D626IF (Ashwagandha) SB - IM MH - Antineoplastic Agents/pharmacology MH - Apoptosis/drug effects MH - Apoptosis Regulatory Proteins/metabolism MH - Bcl-2-Like Protein 11/deficiency/genetics/metabolism MH - Carcinoma, Squamous Cell/*drug therapy/metabolism/pathology MH - Caspase 8/metabolism MH - Caspase 9/drug effects/metabolism MH - Cell Line, Tumor MH - Cytochromes c/metabolism MH - Enzyme Activation/drug effects MH - Head and Neck Neoplasms/*drug therapy/metabolism/pathology MH - Humans MH - Membrane Potential, Mitochondrial/drug effects MH - Mitochondrial Membranes/drug effects MH - Mouth Neoplasms/drug therapy MH - Plant Extracts/*pharmacology MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism MH - Squamous Cell Carcinoma of Head and Neck MH - Up-Regulation MH - Withanolides/pharmacology OTO - NOTNLM OT - Ashwagandha OT - apoptosis OT - head and neck cancer EDAT- 2015/09/04 06:00 MHDA- 2017/01/24 06:00 CRDT- 2015/09/03 06:00 PHST- 2015/07/27 00:00 [accepted] PHST- 2015/09/03 06:00 [entrez] PHST- 2015/09/04 06:00 [pubmed] PHST- 2017/01/24 06:00 [medline] AID - 10.1111/jop.12353 [doi] PST - ppublish SO - J Oral Pathol Med. 2016 Mar;45(3):193-201. doi: 10.1111/jop.12353. Epub 2015 Aug 31.