Previous studies have reported that vitexins induce cytotoxic effects. In the present study, we investigate a new native lignan vitexin 6 (VB6) in vitro to determine the molecular mechanism underlying its cytotoxicity. We screened and cultured several tumor cell lines and subsequently analyzed VB6 cytotoxicity against 14 different tumor cell lines using a 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The expression of proteins that regulate apoptosis and autophagy was determined using western blot analysis. VB6 showed an excellent cytotoxic effect against various cancer cell lines in vitro. It induced apoptosis and autophagy of cancer cells. VB6-induced apoptosis showed a time-dependent and concentration-dependent relationship with cleaved poly (ADP-ribose) polymerase, cleaved caspase-3, Bax upregulation, and Bcl-2 downregulation. The levels of Beclin-1 and LC3-II, which are markers for cell autophagy, gradually increased after VB6 treatment. Jun N-terminal kinase (JNK) phosphorylation was increased after VB6 treatment, accompanied by upregulation of P-Bcl-2 and P-C-Jun expression. Cotreatment with a JNK inhibitor significantly decreased VB6-induced cell death and downregulated P-Bcl-2, and cleaved PARP and Beclin-1 expression. The new native lignan VB6 inhibits cancer cell proliferation by activating the JNK pathway. We believe that VB6 could be a valuable chemotherapeutic drug after further evaluation.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [30973465, 81071879]
第一作者机构:[1]Zhejiang Univ, Sch Med, Dept Surg, Womens Hosp, Hangzhou 310006, Zhejiang, Peoples R China[2]Inst Canc Res, Key Lab Mol Biol Med Sci Zhejiang Prov, China Natl Minist Educ, Key Lab Canc Prevent & Intervent, Hangzhou, Zhejiang, Peoples R China
通讯作者:
通讯机构:[1]Zhejiang Univ, Sch Med, Dept Surg, Womens Hosp, Hangzhou 310006, Zhejiang, Peoples R China[*1]Department of Surgery, Women’s Hospital School of Medicine, Zhejiang University, 1, Xueshi Road, Hangzhou, Zhejiang 310006, China
推荐引用方式(GB/T 7714):
Zhou Jun,Hu Huiyong,Long Jingpei,et al.Vitexin 6, a novel lignan, induces autophagy and apoptosis by activating the Jun N-terminal kinase pathway[J].ANTI-CANCER DRUGS.2013,24(9):928-936.doi:10.1097/CAD.0b013e328364e8d3.
APA:
Zhou, Jun,Hu, Huiyong,Long, Jingpei,Wan, Fang,Li, Lili...&Chen, Yiding.(2013).Vitexin 6, a novel lignan, induces autophagy and apoptosis by activating the Jun N-terminal kinase pathway.ANTI-CANCER DRUGS,24,(9)
MLA:
Zhou, Jun,et al."Vitexin 6, a novel lignan, induces autophagy and apoptosis by activating the Jun N-terminal kinase pathway".ANTI-CANCER DRUGS 24..9(2013):928-936