title: Triptolide exerts pro-apoptotic and cell cycle arrest activity on drug-resistant human lung cancer A549/Taxol cells via modulation of MAPK and PI3K/Akt signaling pathways.
abstract: Multidrug resistance (MDR) is a major obstacle in the effective chemotherapeutic treatment of cancers. Triptolide (TPL) is a diterpenoid isolated fromTripterygium wilfordiiHook. f., a traditional Chinese medicine. It was demonstrated in our previous study that TPL exerts anti-MDR cancers on various MDR cell lines (including A549/Taxol, MCF-7/ADR and Bel7402/5-Fu). The present study was designed to investigate its anti-proliferative activity on A549/Taxol cells, and explore the underlying mechanism of action. The anti-proliferative activity of TPL on A549/Taxol cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Its pro-apoptosis and cell cycle arrest activities were analyzed by flow cytometry. Western blot assay was employed to investigate the levels of mitogen-activated protein kinases (MAPKs) and apoptosis-related proteins in cells. TPL efficiently suppressed the proliferation of A549/Taxol cells. Co-treatment with MAPK inhibitors in the MTT assay indicated that the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways were involved in the process. Upregulation of p-p38, p-ERK, p-GSK-3β, Bax and cleaved caspases-3 and -9, and downregulation of p-JNK, p-Akt and Bcl-2 were observed upon treatment with TPL in the A549/Taxol cells. The results from flow cytometry assay revealed that TPL induced apoptosis and S-phase arrest in A549/Taxol cells. This occurred as a result of the upregulation of p-ERK and p-GSK-3β, and the downregulation of p-JNK and p-Akt, and was responsible for the subsequent anti-proliferative activity.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Chen Qiong
authors.initials: CQ
authors.lastname: Xie
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China; Jiangsu Key Laboratory for Chinese Material Medical Processing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China; Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Jian Wei
authors.initials: JW
authors.lastname: Chen
keywords: PI3K/Akt; S-phase arrest; apoptosis; mitogen-activated protein kinases; multidrug resistance; triptolide