Aqueous Extract of Paris polyphylla (AEPP) Inhibits Ovarian Cancer via Suppression of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator (PGC)-1alpha.

Chia-Woei Wang,Chen-Jei Tai,Bao-Hong Lee,Yu-Chun Lin,Cheng-Jeng Tai,Yeu-Ching Shi,Chen-Yen Choong

doi:10.3390/molecules21060727

Abstract

Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients’ lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP)—a traditional Chinese medicine—can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG) induced-human ovarian carcinoma cell line (OVCAR-3 cells). The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR)-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC-1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration.

Highlights

Paris polyphylla is an established herbal medicine, used in fevers, headaches, burns, wounds, and cancers [1]
Growth of OVCAR-3 cells was suppressed by aqueous extract of Paris polyphylla (AEPP) treatment for 24 h, and the cell viability
Apoptosis and by the annexin-V-FITC/propidium iodide (PI) double staining method, which in combination necrosis induction caused by AEPP treatment in the OVCAR-3 cells was confirmed by the annexinwith flow cytometry enabled assessment ofinviable

Summary

Introduction

Paris polyphylla is an established herbal medicine, used in fevers, headaches, burns, wounds, and cancers [1]. P. polyphylla has been used in Oriental folk medicine for its anticancer activities both in vivo and in vitro [2]. Numerous natural steroidal saponins isolated from herbs show potential apoptosis-promoting activity against several cancer cell lines [3,4,5]. P. polyphylla treatment can inhibit epithelial–mesenchymal transition (EMT) and invasion in breast cancer [6] and lung cancer [3,4]. EMT results in invasive cells entering the blood stream [7]. Cancer stem cells undergo EMT and migrateMolecules to distant organs [8,9]. During EMT, epithelial cells have decreased expression of epithelial

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Conclusion