Title of article :
DHA2, a synthesized derivative of bisbibenzyl, exerts antitumor activity against ovarian cancer through inhibition of XIAP and Akt/mTOR pathway
Author/Authors :
Pang، نويسنده , , Yingxin and Si، نويسنده , , Manfei and Sun، نويسنده , , Bin and Niu، نويسنده , , Leilei and Xu، نويسنده , , Xia and Lu، نويسنده , , Tao and Yuan، نويسنده , , Huiqing and Lou، نويسنده , , Hongxiang، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2014
Pages :
12
From page :
163
To page :
174
Abstract :
The analysis of dihydroptychantol (DHA) and its chemically synthesized macrocyclic bisbibenzyl derivatives (DHA1, 2 and 3) led to the selection of DHA2 as a potential drug candidate for ovarian cancer. The exposure of ovarian cancer SKOV3 cells to DHA2 resulted in the downregulation of the anti-apoptotic X-linked inhibitor of apoptosis protein (XIAP) and Bcl-2 and led to caspase-independent cell death. The overexpression of XIAP reversed DHA2-induced cell death, and the depletion of XIAP had the opposite effect. DHA2 could induce autophagy, as evidenced by increases in the formation of acidic vesicular organelles and the processing of LC3B-I to LC3B-II. Pretreatment with autophagy inhibitors potentiated DHA2-mediated cell death. We showed that typical PI3K/Akt signaling was involved in DHA2-mediated cell death. The overexpression of Akt almost completely reversed DHA2-induced cell death, and the inactivation of Akt significantly facilitated DHA2-induced cell death. The administration of DHA2 to xenograft mice reduced tumor growth by causing Akt inactivation, the conversion of LC3B and proliferation inhibition. Our study demonstrates that the inhibition of XIAP and the inactivation of Akt/mTOR facilitate the efficacy of DHA2 in ovarian cancer cells.
Keywords :
Ovarian cancer , Caspase-independent cell death , Autophagy , Akt , mTOR
Journal title :
Food and Chemical Toxicology
Serial Year :
2014
Journal title :
Food and Chemical Toxicology
Record number :
2126978
Link To Document :
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