Abstract
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. 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. 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. These suggest that MEAG and WA may be potential natural ...Continue Reading
References
Jan 1, 1985·Cancer Chemotherapy and Pharmacology·R P MortonP M Stell
Oct 1, 1995·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·M J McKeage
Feb 1, 1996·Current Opinion in Genetics & Development·S N Farrow, R Brown
Feb 28, 1998·The EMBO Journal·L O'ConnorD C Huang
May 23, 1998·Annual Review of Immunology·D T Chao, S J Korsmeyer
Sep 4, 1998·Cell·X LuoX Wang
Jul 5, 2002·The Journal of Biological Chemistry·Nobuhiro MorishimaYukuto Yasuhiko
Apr 15, 2004·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·M S PariharTaruna Hemnani
Apr 21, 2005·Evidence-based Complementary and Alternative Medicine : ECAM·Bandhuvula PadmavathiRana Pratap Singh
Nov 2, 2007·PLoS Medicine·Daniel B CostaSusumu Kobayashi
Sep 17, 2008·Cancer Research·Silvia D StanShivendra V Singh
Nov 7, 2008·Apoptosis : an International Journal on Programmed Cell Death·Chandan MandalChitra Mandal
Nov 13, 2008·Apoptosis : an International Journal on Programmed Cell Death·Jung Hwa OhTaeg Kyu Kwon
Mar 10, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Fayaz MalikJaswant Singh
May 12, 2009·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Stefania NobiliSergio Capaccioli
Sep 2, 2009·Oral Oncology·Sang-Heng KokMark Yen-Ping Kuo
Jul 28, 2010·Oral Diseases·J-A ShinS-D Cho
Oct 27, 2010·PloS One·Nashi WidodoSunil C Kaul
Mar 8, 2011·Microbial Biotechnology·Arnold L Demain, Preeti Vaishnav
May 13, 2011·The Journal of Biological Chemistry·Juan WangGen Sheng Wu
Sep 11, 2012·Advances in Pharmacology·Anthony C FaberJeffrey A Engelman
Nov 13, 2012·Anaerobe·Santosh PanditJae-Gyu Jeon
Mar 23, 2013·Parasitology Research·Heena SachdevaSukhbir Kaur
Sep 17, 2013·Cell Biochemistry and Function·Hang-Eun LeeSung-Dae Cho
Oct 17, 2013·PloS One·Renu WadhwaSunil C Kaul
Dec 7, 2013·Oral Oncology·Heang-Eun LeeSung-Dae Cho
Jul 25, 2014·European Journal of Pharmacology·Shaloam Dasari, Paul Bernard Tchounwou
Oct 9, 2014·Planta medica·Zsuzsanna HajdúIstván Zupkó
Nov 26, 2014·South Asian Journal of Cancer·Puneet Kumar BagriSatya Narayan
Jan 3, 2015·Journal of Ethnopharmacology·Kheng Leong OoiShaida Fariza Sulaiman
Jan 8, 2015·Neoplasma·T E GoranovaE I Georgieva
Mar 31, 2015·Oral Oncology·Hyun-Ju YuJeong-Sang Lee
Citations
Mar 15, 2016·Cell Biochemistry and Biophysics·Ammad Ahmad FarooqiIlaria Marech
Mar 10, 2016·International Journal of Molecular Sciences·In-Chul Lee, Bu Young Choi
May 17, 2018·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Dong-Hoon WonSung-Dae Cho
Nov 23, 2017·Aging·Alexander AliperAlex Zhavoronkov
May 10, 2020·Cancers·Anissa Nofita SariRenu Wadhwa
Oct 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Su-Jung ChoiSung-Dae Cho
Mar 17, 2020·Journal of Ethnopharmacology·Akash SaggamBhushan Patwardhan
Apr 18, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Abedul HaqueArm R Amin
Aug 7, 2021·Frontiers in Pharmacology·Nikita AggarwalAlok Chandra Bharti