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Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride channels
Lianshun Ma1, Yaping Yang2, Zizhang Yin3
1Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, China; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Abstract:
Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum. Recent studies demonstrated that emodin has anti-cancer activity in different kinds of human cancer cell lines. However, the underlying mechanism has not been very well studied. Our previous studies showed chloride channels is an important target of anti-cancer drugs. Therefore, the purpose of this research was aimed to explore the role of chloride channels involving in the anti-cancer activity of emodin. The proliferation, cell cycle arrest and apoptosis of poorly differentiated human nasopharyngeal carcinoma cells (CNE-2Z) and normal nasopharyngeal epithelial cells (NP69-SV40T) were detected by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT)and flow cytometry. The results indicated that emodin inhibited the CNE-2Z cell growth more significantly than NP69-SV40T cells and induced cell cycle arrest and apoptosis in CNE-2Z cells but not in NP69-SV40T cells. Chloride channel blocker 5-nitro-2-(3-phenylprop ylamino)-benzoate (NPPB) or tamoxifen both can prevent the apoptosis of CNE-2Z cells induced by emodin. Optical microscope and atomic force microscope (AFM) demonstrated that emodin can induce apoptotic volume decrease (AVD) and ultrastructure changes in CNE-2Z cell and inhibited by chloride channel blocker. These data could be a further evidence of chloride channel for preventing CNE-2Z cells from apoptosis induced by emodin. Whole cell patch clamp study also demonstrated that emodin can activate chloride channel in CNE-2Z cells but not in NP69-SV40T cells. Furthermore, the activated chloride currents can also be inhibited by chloride channel blockers indicating that chloride channel may be the potential target molecular of emodin exerting its anti-tumor efficiency in CNE-2Z cells.
Insights
Emodin, a natural compound, shows anti-cancer effects by activating chloride channels in nasopharyngeal carcinoma cells, leading to apoptosis. This mechanism is blocked by specific inhibitors, highlighting chloride channels as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Emodin, a natural anthraquinone derivative, exhibits anti-cancer properties.
- The precise mechanism of emodin's anti-cancer activity remains largely unelucidated.
- Chloride channels are recognized as crucial targets for anti-cancer drug development.
Purpose of the Study:
- To investigate the role of chloride channels in mediating the anti-cancer effects of emodin.
- To explore emodin's impact on cell proliferation, cell cycle, and apoptosis in nasopharyngeal carcinoma cells.
- To determine if chloride channel blockers can modulate emodin-induced anti-cancer responses.
Main Methods:
- Cell viability assays (MTT) and flow cytometry were used to assess proliferation, cell cycle arrest, and apoptosis.
- Human nasopharyngeal carcinoma cells (CNE-2Z) and normal nasopharyngeal epithelial cells (NP69-SV40T) were utilized.
- Chloride channel blockers (NPPB, tamoxifen) and patch-clamp electrophysiology were employed.
Main Results:
- Emodin significantly inhibited CNE-2Z cell growth while sparing normal cells.
- Emodin induced cell cycle arrest and apoptosis in CNE-2Z cells, effects reversed by chloride channel blockers.
- Emodin activated chloride channels in CNE-2Z cells, evidenced by patch-clamp studies and apoptotic volume decrease (AVD).
Conclusions:
- Chloride channels are implicated in emodin's anti-cancer activity against nasopharyngeal carcinoma.
- Emodin's ability to activate chloride channels is a key mechanism for inducing apoptosis in CNE-2Z cells.
- Targeting chloride channels represents a potential therapeutic strategy for nasopharyngeal cancer utilizing emodin.