Anticancer activity of Ashwagandha against human head and neck cancer cell lines.
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.
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.
Haeng-Eun
HE
Lee
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.
Ji-Ae
JA
Shin
Department of Dermatology and Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA.
Joseph H
JH
Jeong
Department of Preventive Dentistry, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea.
Jae-Gyu
JG
Jeon
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.
Min-Ho
MH
Lee
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.
Sung-Dae
SD
Cho
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D015854:Up-Regulation; D054358:Withanolides / Q000494:pharmacology
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D010936:Plant Extracts; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; D054358:Withanolides; D045304:Cytochromes c; D053181:Caspase 8; D053453:Caspase 9; C009684:withaferin A; C030693:Ashwagandha
Ashwagandha; apoptosis; head and neck cancer