Abstract
Withaferin A (WA) is a bioactive compound derived from Withania somnifera. The antitumor activity of WA has been well studied in human cancer models; however, its chemopreventive potential is unclear. In the present study, we used the skin epidermal JB6 P+ cells, a well-established model for tumor promotion, and demonstrated that WA suppressed the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell transformation and cell proliferation. Interestingly, TPA inactivated isocitrate dehydrogenase 1 (IDH1), which was reversed by WA. Similar results were also observed in mouse skin tissue. Therefore, we focused on metabolism as the potential mechanism of action. We found that mitochondrial functions were downregulated by TPA treatment, as indicated by reduced mitochondrial membrane potential, complex I activity and mitochondrial respiration. However, all of these downregulations were inhibited by WA. In addition, we examined the levels of α-ketoglutarate, a product of IDH1, and WA blocked its reduction upon TPA treatment. Finally, we detected the lactate level as a glycolysis marker, and WA suppressed its elevation caused by tumor promoter treatment. Altogether, these results suggest that WA might exert its chemopre...Continue Reading
References
Oct 18, 1979·Nature·N H ColburnS H Yuspa
Sep 1, 1996·The Journal of Clinical Investigation·H C YenD K St Clair
Nov 7, 1998·Nature Genetics·K PolyakB Vogelstein
Sep 3, 2002·Environmental Health Perspectives·Kazumi SuzukawaNancy H Colburn
Feb 24, 1956·Science·O WARBURG
Mar 21, 2006·Free Radical Biology & Medicine·Yunfeng ZhaoDaret St Clair
May 23, 2006·Cell·Ramin MassoumiReinhard Fässler
Jun 13, 2006·Cancer Cell·Valeria R FantinPhilip Leder
Aug 8, 2006·Oncogene·A KingE Gottlieb
Dec 23, 2006·Cancer Research·Sowmyalakshmi SrinivasanDamodaran Chendil
Jun 23, 2007·Chemistry & Biology·Paola Bargagna-MohanRoyce Mohan
Jan 4, 2008·Molecular Cancer Research : MCR·Jerry LuJohn Digiovanni
Feb 13, 2008·Free Radical Biology & Medicine·Magdalena L CircuTak Yee Aw
Jun 4, 2008·The Journal of Biological Chemistry·Nam Joo KangZigang Dong
Sep 6, 2008·Science·D Williams ParsonsKenneth W Kinzler
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
Nov 15, 2008·Nutrition and Cancer·Silvia D StanShivendra V Singh
Dec 4, 2008·Molecular Nutrition & Food Research·Numsen Hail, Reuben Lotan
Feb 5, 2009·Integrative Cancer Therapies·Guruprasad KalthurUma Devi Pathirissery
Feb 21, 2009·The New England Journal of Medicine·Hai YanDarell D Bigner
Apr 11, 2009·Science·Shimin ZhaoYue Xiong
Jul 7, 2009·Cancer Science·Navjot ShahRenu Wadhwa
Aug 7, 2009·The New England Journal of Medicine·Elaine R MardisTimothy J Ley
Aug 19, 2009·Molecular and Cellular Biology·'Matladi N NdlovuWim Vanden Berghe
Sep 23, 2009·Biochemical Pharmacology·Yanke YuDuxin Sun
Oct 24, 2009·Circulation Research·Zhongping LuMichael N Sack
Jan 8, 2010·Molecular Cancer Therapeutics·Srinivas KoduruChendil Damodaran
Apr 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Frank WeinbergNavdeep S Chandel
Jun 19, 2010·Nature·Lenny DangShinsan M Su
Jan 25, 2011·Nature Reviews. Cancer·Rob A CairnsTak W Mak
Jun 16, 2011·Cancer Prevention Research·Jennifer A WittwerYunfeng Zhao
Apr 27, 2012·Cancer Science·Delira RobbinsYunfeng Zhao
Citations
Apr 8, 2015·Pharmaceutical Biology·Mahendra RaiCarolina Alves dos Santos
Oct 17, 2015·Molecular Carcinogenesis·Wenjuan LiYunfeng Zhao
Jun 25, 2015·Carcinogenesis·Wilhelm EngströmWilliam H Bisson
Aug 21, 2018·Carcinogenesis·Balaji ChandrasekaranChendil Damodaran
Jun 2, 2020·Pharmaceutical Biology·Ziyi GuanBinyao Shou
Jul 17, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Fangfang TaoZhiqian Zhang
Mar 17, 2020·Journal of Ethnopharmacology·Akash SaggamBhushan Patwardhan
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Simona BungauLaura Endres