Secalonic acid D induces cell apoptosis in both sensitive and ABCG2-overexpressing multidrug resistant cancer cells through upregulating c-Jun expression

• 来源期刊: 药学学报（英文版）
• 关键词: Multidrug resistance Secalonic acid D Apoptosis c-Jun ABCG2
• 年，卷（期）: 2019,（3）
• 页码范围: 516-525
• 页数: 10页
• 语种: 英文

摘要

Secalonic acid D (SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant (MDR) cells.However,the molecular mechanisms need to be elucidated.Here,we identified that SAD possessed potent cytotoxicity in 3 pairs of MDR and their parental sensitive cells including S1-MI-80 and S1,H460/MX20 and H460,MCF-7/ADR and MCF-7 cells.Furthermore,SAD induced cell G2/M phase arrest via the downregulation of cyclin B1 and the increase of CDC2 phosphorylation.Importantly,JNK pathway upregulated the expression of c-Jun in protein level and increased c-Jun phosphorylation induced by SAD,which was linked to cell apoptosis via c-Jun/Src/STAT3 pathway.To investigate the mechanisms of upregulation of c-Jun protein by SAD,the mRNA expression level and degradation of c-Jun were examined.We found that SAD did not alter the mRNA level of c-Jun but inhibited its proteasome-dependent degradation.Taken together,these results implicate that SAD induces cancer cell death through c-Jun/Src/STAT3 signaling axis by inhibiting the proteasome-dependent degradation of c-Jun in both sensitive cells and ATP-binding cassette transporter sub-family G member 2 (ABCG2)-mediated MDR cells.