Apoptosis induction of dehydrobruceine B on two kinds of human lung cancer cell lines through mitochondrial-dependent pathway

BackgroundBrucea javanica is an effective traditional medicine listed in Chinese Pharmacopoeia. In China, the seed oil of B. javanica has long been used as commercially available drug for the treatment of tumor in clinic. Dehydrobruceine B (DHB) is a quassinoid isolated from B. javanica.PurposeThe aim of the present study is to investigate the apoptotic effects induced by DHB in human lung cancer A549 and NCI-H292 cells. The involvement of a mitochondria-mediated intrinsic pathway in the pro-apoptotic action of DHB was also investigated.Material and methodsCell viability was determined by MTT assay. Cell cycle and apoptosis were assessed by flow cytometry analysis. Mitochondrial membrane potential (MMP) was examined through JC-1 staining. The protein translocation in cells was examined by immunostaining. The expression levels of proteins which are closely related to mitochondria-mediated apoptosis pathway were measured by immunoblot analysis.ResultsTreatment with DHB decreased cell viability, induced apoptosis and blocked cell cycle at S phase. DHB-induced apoptosis was found to be mediated through mitochondrial intrinsic pathway, evidenced by the loss of MMP, the release of cytochrome c into cytosol, and the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP).ConclusionDHB triggers apoptosis in A549 and NCI-H292 cells via mitochondrial pathway, making it a promising candidate as a therapeutic agent for lung carcinoma.

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