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Cell Biol Int. 2018 Sep;42(10):1377-1385. doi: 10.1002/cbin.11023. Epub 2018 Jul 23.

β-elemene increases the sensitivity of gastric cancer cells to TRAIL by promoting the formation of DISC in lipid rafts.

Xu L1,2, Guo T1,2, Qu X1,2, Hu X3, Zhang Y1,2, Che X1,2, Song H1,2, Gong J1,2, Ma R1,2, Li C1,2, Fan Y1,2, Ma Y1,2, Hou K1,2, Wu P1,2, Dong H1,2, Liu Y1,2.

Author information

1
Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, China.
2
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China.
3
Department of Respiratory and Infectious Disease of Geriatrics, the First Hospital of China Medical University, Shenyang, 110001, China.

Abstract

β-Elemene, an anti-cancer drug extracted from traditional Chinese medicinal herb, showed anti-tumor effects on gastric cancer cells. Our previous studies reported gastric cancer cells are insensitive to TRAIL. However, whether β-elemene could enhance anti-cancer effects of TRAIL on gastric cancer cells is unknown. In our present study, β-elemene prevented gastric cancer cell viability in dose-dependent manner, and when combined with TRAIL, obviously inhibited proliferation and promoted apoptosis in gastric cancer cells. Compared to β-elemene or TRAIL alone, treatment with β-elemene and TRAIL obviously promoted DR5 clustering as well as translocation of Caspase-8, DR5 and FADD into lipid rafts. This led to cleavage of Caspase-8 and the formation of death-inducing signaling complex (DISC) in lipid rafts. The cholesterol-sequestering agent nystatin partially reversed DR5 clustering and DISC formation, preventing apoptosis triggered by the combination of β-elemene and TRAIL. Our results suggest that β-elemene increases the sensitivity of gastric cancer cells to TRAIL partially by promoting the formation of DISC in lipid rafts.

KEYWORDS:

DISC; TRAIL; apoptosis; gastric cancer; β-elemene

PMID:
29957841
DOI:
10.1002/cbin.11023
[Indexed for MEDLINE]

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