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Rhein lysinate inhibits cell growth by modulating various mitogen-activated protein kinases in cervical cancer cells
Yong-Zhan Zhen1, Ya-Jun Lin, Jun-Ling Gao
1North China Coal Medical University, Tangshan, Hebei 063000.
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.
Insights
Rhein lysinate (RHL) effectively inhibits human cervical cancer (HeLa) cell growth and induces apoptosis. RHL activates specific cell signaling pathways, showing potential as a cervical cancer therapeutic.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Rhein lysinate (RHL), a water-soluble salt of rhein and lysine, has demonstrated anti-tumor properties against various cancers.
- Previous research indicated RHL's efficacy in inhibiting breast, ovarian, and liver cancer cell growth.
Purpose of the Study:
- To investigate the anti-proliferative effects of RHL on human cervical carcinoma HeLa cells.
- To elucidate the underlying molecular mechanisms responsible for RHL-induced growth inhibition and apoptosis.
Main Methods:
- HeLa cells were treated with varying doses and durations of RHL.
- Apoptosis was assessed by measuring cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7 levels.
- Key signaling pathways, including p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), and extracellular signal-related kinase (ERK), were analyzed.
Main Results:
- RHL significantly inhibited HeLa cell growth in a dose- and time-dependent manner.
- RHL induced apoptosis in HeLa cells, evidenced by increased cleaved PARP and caspase-3/7.
- RHL-induced apoptosis was mediated by the activation of p38 MAPK and JNK, while ERK activation was increased, and its inhibition enhanced RHL's effect.
Conclusions:
- Rhein lysinate exhibits potent anti-cancer activity against human cervical carcinoma cells.
- RHL triggers apoptosis through the activation of p38 MAPK and JNK signaling pathways.
- RHL represents a promising candidate for the development of novel chemotherapeutic agents for cervical cancer treatment.
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