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J Asian Nat Prod Res. 2012;14(11):1008-19. doi: 10.1080/10286020.2012.693481.

p38-NF-κB-promoted mitochondria-associated apoptosis and G2/M cell cycle arrest in norcantharidin-treated HeLa cells.

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1
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.

Abstract

Previous study proved that norcantharidin (NCTD) could exert its anticancer activity in a variety of malignant cell lines, including human cervical carcinoma HeLa cells. In this study, we found that NCTD-activated p38 mitogen-activated protein kinase (p38 MAPK)-nuclear transcription factor kappa B (NF-κB) signaling pathway induced mitochondrial apoptotic pathway activation and G2/M cell cycle arrest in HeLa cells. NCTD-induced mitochondria-associated apoptosis was concomitant with the collapse of mitochondrial membrane potential (ΔΨ(m)), translocation of Bax, down-regulation of Bcl-2 expression, and release of cytochrome c. NCTD-led G2/M cell-cycle arrest was associated with the up-regulated p21 and p-cdc25c expression and the down-regulated cyclin B and cdc2 expression. Treatment of the cells with p38 inhibitor SB203580 and NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) showed that p38 functioned upstream of NF-κB, while augmented apoptosis and cell cycle arrest were induced in response to NCTD with NF-κB activation. Intriguingly, NF-κB had a negative feedback regulatory effect on p38 activation. Moreover, NCTD-induced apoptosis and cell cycle arrest were significantly blocked by SB203580 and PDTC but not by pifithrin-α (p53 inhibitor). Therefore, p38-NF-κB induced mitochondrial apoptotic pathway and G2/M cell cycle arrest in NCTD-treated HeLa cells.

PMID:
23281704
DOI:
10.1080/10286020.2012.693481
[Indexed for MEDLINE]
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