title: p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy.
abstract: Dihydroartemisinin (DHA) exhibits anticancer activities in a variety of cancer cells, but DHA alone are not effective enough for cancer therapy. In this study we found the stress-regulated protein p8 was obviously increased after DHA treatment in several cancer cells, which further to induce autophagy by the upregulation of endoplasmic reticulum stress-related protein ATF4 and CHOP. Furthermore, when we silenced p8 by siRNA in cancer cells, the apoptosis induced by DHA were notably increased, whereas the overexpression of p8 in cancer cells leaded to the resistance to DHA-induced apoptosis. Moreover, we found the inhibition of autophagy with chloroquine (CQ) can enhance the anticancer effect of DHA both in vitro and in vivo. In conclusion, we found that p8-mediated autophagy attenuates DHA-induced apoptosis in cancer cells, which provides evidence to support the use p8 as a cancer therapeutic target, and suggests that the combination treatment with DHA and autophagy inhibitor might be an effective cancer therapeutic strategy.
authors.affiliation: a Institute of Pharmacology and Toxicology; College of Pharmaceutical Sciences; Zhejiang University ; Hangzhou , PR China.
authors.forename: Sang-Sang
authors.initials: SS
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Zeng
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiao-E
authors.initials: XE
authors.lastname: Lou
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Zhou
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D017209:Apoptosis; D037621:Artemisinins / Q000627:therapeutic use*; D001343:Autophagy; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D051792:Basic Helix-Loop-Helix Proteins; D009363:Neoplasm Proteins; C491643:NUPR1 protein, human; C039060:artenimol
keywords: AO Acridine orange; ART artemisinin; ATF4 activating transcription factor 4; AVOs acidic vesicular organelles; CHOP C/EBP homologous protein; CQ chloroquine; DHA dihydroartemisinin; ERs endoplasmic reticulum stress; MDC Dansylcadaverine; autophagy; chloroquine; dihydroartemisinin; endoplasmic reticulum stress; p8