Rhein lysinate inhibits cell growth by modulating various mitogen-activated protein kinases in cervical cancer cells

Zhen,Yong-Zhan; Lin,Ya-Jun; Gao,Jun-Ling; Zhao,Yu-Fang; Xu,Ai-Jun

doi:10.3892/ol.2010.200

Rhein lysinate inhibits cell growth by modulating various mitogen-activated protein kinases in cervical cancer cells

Authors:
- Yong-Zhan Zhen
- Ya-Jun Lin
- Jun-Ling Gao
- Yu-Fang Zhao
- Ai-Jun Xu
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Affiliations: North China Coal Medical University, Tangshan, Hebei 063000, P.R. China, The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, P.R. China
Published online on: November 1, 2010 https://doi.org/10.3892/ol.2010.200
Pages: 129-133

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Abstract

In previous studies, we found that rhein lysinate (RHL; the salt of rhein and lysine, easily dissolved in water) inhibited the growth of tumor cells in breast and ovarian cancer and hepatocellular carcinoma. This study aimed to investigate the effect of RHL on the growth of human cervical carcinoma HeLa cells and any underlying mechanisms. RHL inhibited the growth of HeLa cells in a dose- and time-dependent manner. It was also noted that RHL induced apoptosis in HeLa cells in a dose-dependent manner. Mechanistically, RHL triggered HeLa cell apoptosis by increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7. In addition, the activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was a critical mediator in RHL-induced growth inhibition. Inhibition of the expression of p38 MAPK and JNK by pharmacological inhibitors reversed RHL-induced growth inhibition by decreasing the level of cleaved PARP and caspase-3/7. Phosphorylation of the extracellular signal-related kinase (ERK) was increased by RHL; conversely, the MEK inhibitor which inhibits ERK activity, synergistically enhanced RHL-induced growth inhibition in HeLa cells. The results showed that RHL inhibits Hela cell growth through the activation of p38 MAPK and JNK, and is a potential chemotherapeutic agent for cervical cancer.

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