Abstract
Shikonin (SK), a naturally occurring naphthoquinone, exhibits antitumor activity. However, its precise mechanisms of action are unknown. In the present study, the effects of SK on NCI-H460 human lung cancer cells were investigated. It was found that SK reduced cell viability and induced apoptosis in the NCI-H460 cells. Additionally, SK inhibited extracellular signal-regulated kinase (ERK) activity, which indicates that inhibition of the ERK pathway is probably one of the mechanisms by which SK induced NCI-H460 cell apoptosis. The expression of Cbl-b was significantly increased by treatment with SK for 4 h, and gradually increased to a maximal level at 24 h; the time taken for the upregulation of Cbl-b protein was in accordance to that required for the downregulation of phospho (p)-ERK protein. The Cbl inhibitor Ps341 reversed the SK-induced downregulation of p-ERK and apoptosis of NCI-H460 cells. These results indicate that Cbl-b potentiates the apoptotic action of SK by inhibiting the ERK pathway in lung cancer cells.
References
Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
Jan 5, 2002·Carcinogenesis·Hemant K RoyThomas C Smyrk
Aug 26, 2003·Antimicrobial Agents and Chemotherapy·Xin ChenO M Zack Howard
Jun 3, 2006·Journal of Cellular Physiology·Gayathri Swaminathan, Alexander Y Tsygankov
Mar 6, 2007·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Daiki MurakamiMasahide Ikeguchi
Mar 5, 2008·Molecular and Cellular Biology·Steven Pennock, Zhixiang Wang
Oct 7, 2008·Journal of Ethnopharmacology·Yu Wen ChengJaw Jou Kang
Jan 24, 2009·International Journal of Cancer. Journal International Du Cancer·Huanjie YangJinbao Liu
May 22, 2009·Cancer Letters·Yingchun LiYunpeng Liu
Nov 12, 2009·British Journal of Cancer·E J DeanC Dive
Feb 6, 2010·The Journal of Biological Chemistry·Christine B F ThienWallace Y Langdon
May 13, 2010·Biological & Pharmaceutical Bulletin·I-Chang ChangLi-Sung Hsu
Dec 18, 2010·Canadian Journal of Physiology and Pharmacology·Nie YingkunYu Huimin
Jan 22, 2011·Journal of Asian Natural Products Research·Hong-Ming ChengYu-Fen Zhao
Jun 10, 2011·Communicative & Integrative Biology·Mayumi NaramuraHamid Band
Jul 5, 2011·Cancer Biology & Therapy·Jinglei QuYunpeng Liu
Nov 3, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·Benjamin WienchThomas Efferth
Jun 14, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Ting LiLiang Liu
Oct 2, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Chibo LiuJiayu Chen
Jan 28, 2014·Chemico-biological Interactions·Mu-Jang LeeLi-Sung Hsu
Citations
Jul 28, 2016·Biochimica Et Biophysica Acta·Yun-Ji JeungKyung-Sook Chung
Nov 13, 2013·Neuropeptides·M J Zaben, W P Gray
Jul 5, 2018·Cell Biology International·Tieqiong ZhangXuejun Hu
Jul 30, 2016·Oncotarget·Minakshi Nihal, Gary S Wood
Nov 14, 2019·Chinese Medicine·Hua LuoYitao Wang