Open AccessTanshinone IIA induces cell death via Beclin‐1‐dependent autophagy in oral squamous cell carcinoma SCC ‐9 cell line
Author(s) -
Qiu Ye,
Li Conghua,
Wang Qinhua,
Zeng Xingqi,
Ji Ping
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1281
Subject(s) - atg5 , autophagy , apoptosis , pi3k/akt/mtor pathway , atg12 , cancer research , chemistry , salvia miltiorrhiza , protein kinase b , programmed cell death , cell growth , cell culture , cell , microbiology and biotechnology , biology , medicine , pathology , biochemistry , genetics , alternative medicine , traditional chinese medicine
Tanshinone IIA ( TAN ) is one of the major functional compounds of Salvia miltiorrhiza Bunge and possesses the ability to suppress the growth of multiple cancer cell types via its apoptosis‐ and autophagy‐inducing functions. In this study, the effect of TAN therapy on the survival of oral squamous cell carcinoma ( OSCC ) was evaluated, and the underlying mechanism involved in the treatment was investigated. Human oral squamous cell carcinoma cell SCC ‐9 was used for in vitro assays and induction in an OSCC xenograft mouse model. The tumor cells were subjected to TAN administration at different concentrations. Then the apoptosis and autophagy processes in SCC ‐9 cells were evaluated and the activities of Beclin‐1/Atg7/Atg12‐Atg5 and PI 3K/Akt/ mTOR pathways were determined. In addition, by knocking down the expression of Beclin‐1 in SCC ‐9 cells, the study also assessed the role of the indicator in the anti‐ OSCC effect of TAN . Results of in vitro assays were further validated with an OSCC xenograft mouse model. Administration of TAN ‐induced cell apoptosis and upregulated the expression of cleaved‐caspase‐3. Simultaneously, the autophagy process in SCC ‐9 cells was initiated by TAN , which was signaled by the formation of autophagosomes and increase in the ratio of LC 3 II / LC 3I. The above processes were associated with the activation of Beclin‐1/Atg7/Atg12‐Atg5 signaling and inhibition of PI 3K/Akt/ mTOR signaling. Our results also inferred a partially Beclin‐1‐dependent mechanism of action of TAN in OSCC cells: knockdown of the Beclin‐1 blocked the effect of TAN on SCC ‐9 cells both in vivo and in vitro. Our study provided a preliminary explanation of the mechanism involved in TAN effect: the agent exerted its autophagy‐inducing effect against OSCC in a multipronged manner, by both inducing the Beclin‐1/Atg7/Atg12‐Atg5 pathway and suppressing the PI 3K/Akt/ mTOR pathway.