PMID- 29545863 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 15 IP - 4 DP - 2018 Apr TI - Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF-7 cells. PG - 3413-3419 LID - 10.3892/etm.2018.5830 [doi] AB - To investigate the effects of triptolide (TPI) on proliferation, autophagy and death in human breast cancer MCF-7 cells, and to elucidate the associated molecular mechanisms, intracellular alterations were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The results of the MTT assay revealed that TPI significantly reduced the MCF-7 cell survival rate when the concentration was >10 nmol/l. TPI activated a caspase cascade reaction by regulating Bcl-2-associated X protein (Bax), caspase-3 and B-cell lymphoma 2 expression, and promoted programmed cell death via the mitochondrial pathway. The results demonstrated that TPI significantly reduced the cell proliferation rate and viability in a time- and dose-dependent manner, which was confirmed by western blotting and immunofluorescent staining. TPI induced autophagy and influenced p38 mitogen-activated protein kinases, extracellular signal-regulated kinase (Erk)1/2, and mammalian target of rapamycin (mTOR) phosphorylation, which resulted in apoptosis. When cells were treated with a combination of TPI and the Erk1/2 inhibitor U0126, the downregulation of P62 and upregulation of Bax were inhibited, which demonstrated that the inhibition of Erk1/2 reversed the autophagy changes induced by TPI. The results indicated that Erk1/2 activation may be a novel mechanism by which TPI induces autophagy and apoptosis in MCF-7 breast cancer cells. In conclusion, TPI affects the proliferation and apoptosis of MCF-7 cells, potentially via autophagy and p38/Erk/mTOR phosphorylation. The present study offers a novel view of the mechanisms by which TPI regulates cell death. FAU - Gao, Huan AU - Gao H AD - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China. AD - School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China. FAU - Zhang, Yue AU - Zhang Y AD - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China. FAU - Dong, Lei AU - Dong L AD - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China. FAU - Qu, Xiao-Yu AU - Qu XY AD - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China. FAU - Tao, Li-Na AU - Tao LN AD - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China. FAU - Zhang, Yue-Ming AU - Zhang YM AD - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China. FAU - Zhai, Jing-Hui AU - Zhai JH AD - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China. FAU - Song, Yan-Qing AU - Song YQ AD - Department of Pharmacy, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China. LA - eng PT - Journal Article DEP - 20180201 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC5841063 OTO - NOTNLM OT - apoptosis OT - autophagy OT - breast cancer OT - extracellular signal-regulated kinase OT - mechanism OT - triptolide EDAT- 2018/03/17 06:00 MHDA- 2018/03/17 06:01 PMCR- 2018/02/01 CRDT- 2018/03/17 06:00 PHST- 2017/09/07 00:00 [received] PHST- 2018/01/24 00:00 [accepted] PHST- 2018/03/17 06:00 [entrez] PHST- 2018/03/17 06:00 [pubmed] PHST- 2018/03/17 06:01 [medline] PHST- 2018/02/01 00:00 [pmc-release] AID - ETM-0-0-5830 [pii] AID - 10.3892/etm.2018.5830 [doi] PST - ppublish SO - Exp Ther Med. 2018 Apr;15(4):3413-3419. doi: 10.3892/etm.2018.5830. Epub 2018 Feb 1.