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Int. J. Mol. Sci. 2016, 17(8), 1244; doi:10.3390/ijms17081244

Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro

1
School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 6 Wangjingzhonghuan South Road, Chaoyang District, Beijing 100102, China
2
Pharmacogenetics, HD Biosciences, Co., Ltd., 590 Ruiqing Road, Zhangjiang Hi-Tech Park East Campus, Pudong New Area, Shanghai 201201, China
3
Technical Department, ACEA Biosciences Inc., No. 5 Sandunxiyuan Road, Hangzhou 310030, China
4
Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China
*
Authors to whom correspondence should be addressed.
Academic Editors: Ge Zhang, Aiping Lu and Hailong Zhu
Received: 30 May 2016 / Revised: 14 July 2016 / Accepted: 15 July 2016 / Published: 2 August 2016
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
View Full-Text   |   Download PDF [2761 KB, uploaded 2 August 2016]   |  

Abstract

Endothelin-1 (ET-1) autocrine and paracrine signaling modulate cell proliferation of tumor cells by activating its receptors, endothelin A receptor (ETAR) and endothelin B receptor (ETBR). Dysregulation of ETAR activation promotes tumor development and progression. The potential of ETAR antagonists and the dual-ETAR and ETBR antagonists as therapeutic approaches are under preclinical and clinical studies. Salvianolic acid A (Sal A) is a hydrophilic polyphenolic derivative isolated from Salvia miltiorrhiza Bunge (Danshen), which has been reported as an anti-cancer and cardio-protective herbal medicine. In this study, we demonstrate that Sal A inhibits ETAR activation induced by ET-1 in both recombinant and endogenous ETAR expression cell lines. The IC50 values were determined as 5.7 µM in the HEK293/ETAR cell line and 3.14 µM in HeLa cells, respectively. Furthermore, our results showed that Sal A suppressed cell proliferation and extended the doubling times of multiple cancer cells, including HeLa, DU145, H1975, and A549 cell lines. In addition, Sal A inhibited proliferation of DU145 cell lines stimulated by exogenous ET-1 treatment. Moreover, the cytotoxicity and cardio-toxicity of Sal A were assessed in human umbilical vein endothelial cells (HUVEC) and Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which proved that Sal A demonstrates no cytotoxicity or cardiotoxicity. Collectively, our findings indicate that Sal A is a novel anti-cancer candidate through targeting ETAR. View Full-Text
Keywords: Salvianolic acid A; endothelin A receptor; anticancer; antagonist; cardiotoxicity Salvianolic acid A; endothelin A receptor; anticancer; antagonist; cardiotoxicity
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Zhang, Q.; Wang, S.; Yu, Y.; Sun, S.; Zhang, Y.; Zhang, Y.; Yang, W.; Li, S.; Qiao, Y. Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro. Int. J. Mol. Sci. 2016, 17, 1244.

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