Protein tyrosine kinase, JNK, and ERK involvement in pseudolaric acid B-induced apoptosis of human breast cancer MCF-7 cells

Acta Pharmacologica Sinica
Jing hua YuTakashi Ikejima

Abstract

To investigate the apoptotic mechanism of pseudolaric acid B (PAB) in human breast cancer MCF-7 cells. 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide analysis and morphological changes were applied to detect apoptosis. The percentage of apoptotic and necrotic cells were calculated by the lactate dehydrogenase activity-based cytotoxicity assay, and the protein expression was examined by Western blot analysis. PAB and/or the mitogen-activated protein kinases, including p38, c-Jun-N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), did not participate in necrosis. P38 had no obvious function on apoptosis after 4 micromol/L PAB treatment for 36 h, but PAB induced JNK phosphorylation and inhibited ERK phosphorylation in the apoptotic process. In this study the inhibitor of protein tyrosine kinase (PTK) genistein inverted the inhibitory effect of PAB, instead promoting the survival of MCF-7 cells. Like genistein, another PTK inhibitor AG1024 had a similar effect on PAB-treated MCF-7 cells, indicating that PAB activated PTK to induce apoptosis. Together with PAB, genistein increased the expression of p-ERK, and decreased the expressions of JNK and p-JNK in PAB-treated MCF-7 cells at 36 h. And it is ...Continue Reading

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Citations

Mar 24, 2009·Acta Pharmacologica Sinica·Ai-guo Meng, Ling-ling Jiang
May 1, 2013·International Journal of Medical Sciences·Jing hua YuXiao fang Yu
Feb 9, 2012·Journal of Cancer Research and Clinical Oncology·Li HouJing-Rong Cui
Oct 25, 2012·Expert Opinion on Investigational Drugs·Min HuangYi-Tao Wang
Oct 16, 2015·Molecular Medicine Reports·Jinghua YuXiao-Fang Yu
Jul 11, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·Muhammad KhanTonghui Ma
Mar 6, 2012·Phytotherapy Research : PTR·Shuli ManChangxiao Liu
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Nov 24, 2016·Oncology Reports·Jinghua YuShucheng Hua
Nov 20, 2013·Molecular Medicine Reports·Tingting Guan, Yanmin Yang
Aug 31, 2018·Frontiers in Cellular and Infection Microbiology·Zengyan WangJinghua Yu
Oct 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Su-Jung ChoiSung-Dae Cho

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis