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Tanshinone I Induces Apoptosis and Pro-Survival Autophagy in Gastric Cancers

Xiaoping Jing, Yichun Xu, Weiwei Cheng, Sheng Guo, Ya Zou, Li He

Cancer Chemother Pharmacol. 2016 Jun;77(6):1171-81.

PMID: 27100736

Abstract:

Purpose:
To investigate the occurrence of apoptosis and autophagy on human gastric cancer cells after treatment by Tanshinone I, as well as the relationship between them.
Methods:
BGC823 and SGC7901 cells were treated with Tanshinone I; the cell proliferation was measured using CCK-8 and clone formation assay; and the expression of apoptosis- and autophagy-associated proteins was detected by Western blot. Autophagic vacuoles in cells were observed with LC3 dyeing using confocal fluorescent microscopy, and apoptotic cells were detected via flow cytometry. Bcl-2 was overexpressed in gastric cells treated with Tanshinone I or not, and autophagy relative protein was investigated; the interaction between Beclin-1 and Bcl-2 was detected by immunoprecipitation. Cell apoptosis was detected when autophagy was inhibited by ATG7-siRNA. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice.
Results:
Tanshinone I inhibited the proliferation of BGC823 and SGC7901 cells, and induced cell apoptosis by inhibiting anti-apoptosis protein Bcl-2. Tanshinone I also increased the conversion of LC3I to LC3II and triggered autophagosome formation, without changing the expression of Beclin-1. However, the Beclin-1 VPS34 complexes were increased after Tanshinone I treatment via inhibiting Bcl-2 expression. Moreover, disturbing autophagy by knockdown of ATG7 expression contributed to Tanshinone I-induced apoptosis. In vivo assay showed that combination with autophagy inhibitor chloroquine in nude mice bearing BGC823 xenograft significantly augmented the antitumor effect of Tanshinone I.
Conclusions:
Tanshinone I induced apoptosis and pro-survival autophagy via inhibiting Bcl-2 expression on gastric cancer, and the combination of chloroquine and Tanshinone I could inhibit tumor growth more efficiently than monotherapy, which might be considered as an effective strategy for the treatment for gastric cancer.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP568730 Tanshinone I Tanshinone I 568-73-0 Price
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