Journal
CANCER SCIENCE
Volume 109, Issue 6, Pages 1889-1901Publisher
WILEY
DOI: 10.1111/cas.13616
Keywords
apoptosis; autophagy; endoplasmic reticulum stress; lung adenocarcinoma; beta,beta-dimethylacrylshikonin
Categories
Funding
- National Natural Science Foundation of China [81403143]
- Excellent Youth Talent Program of Zhejiang Provincial Hospital of Traditional Chinese Medicine [2D01417]
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beta,beta-Dimethylacrylshikonin (DMAS) is an anti-cancer compound extracted from the roots of Lithospermum erythrorhizon. The present study aims to investigate theeffects of DMAS on human lung adenocarcinoma cells invitro and explore the mechanisms of its anti-cancer action. We showed that DMAS markedly inhibited cell viability in a dose- and time-dependent way, and induced apoptosis as well as autophagy in human lung adenocarcinoma cells. Furthermore, we found that DMAS stimulated endoplasmic reticulum stress and mediated autophagy through the PERK-eIF2-ATF4-CHOP and IRE1-TRAF2-JNK axes of the unfolded protein response in human lung adenocarcinoma cells. We also showed that the autophagy induced by DMAS played a prosurvival role in human lung adenocarcinoma cells and attenuated the apoptotic cascade. Collectively, combined treatment of DMAS and pharmacological autophagy inhibitors could offer an effective therapeutic strategy for lung adenocarcinoma treatment.
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