As a type of breast cancer with poorest prognosis and high relapse rate, the triple-negative breast cancer (TNBC) is characterized with no expressions of the genes of estrogen receptor (ER), progesterone receptor (PR) and Her2/neu. And because most chemotherapy need to target at one of the three receptors, the lack of gene expressions in TNBC has made it difficult to treat and often require combinatorial therapies. Now, some compounds extracted from Chinese herbs, e.g., oridonin, are been approved more effective and safer in TNBC treatments.

Oridonin, an extraction from Rabdosia rubescens, are featured with a broad spectrum on both pharmacological and physiological effects, e.g., anti-inflammation, anti-biosis and anti-cancer. However, its disadvantages, e.g., high effective concentrations, poor water solubility, and rapid plasma clearance have greatly hampered its clinical application. Therefore, it is important to find novel possible oridonin analogs in TNBC clinical treatment. 

Recently, by collaborating with Prof. Jia ZHOU, University of Texas Medical Branch, US, the research team of Prof. Ce-Shi CHEN, Kunming Institute of Zoology, CAS, indentified an analog of oridonin, CYD-6-28, which has the potential to be developed as a therapeutic agent to treat TNBC.

In this study, a compound library of novel oridonin derivatives via convergent spectrometry and stereo-controlled synthesis with the aid of nuclear magnetic resonance, mass spectrometry and X-ray techniques were constructed. The activities of series of oridonin analogs against HCC1806 and HCC1937 TNBC cell lines were evaluated. It was indentified that CYD-6-28 has superior aqueous solubility and better cell permeability; inhibits the proliferation of TNBC and induces cell cycle arrest at the G2/M phase and apoptosis; exhibits a greater than 10-fold increase in efficacy compared with the natural product oridonin. Moreover, the molecular mechanisms were also discussed.

These findings reveal the great potential of CYD-6-28 to be developed into a novel anti-TNBC agent. The study is positive in promoting the modernization of Chinese traditional medicines. The main findings of this study have been published on Cancer Letters (http://www.cancerletters.info/article/S0304-3835(16)30393-7/pdf).

Contact Information:

Ce-Shi CHEN

E-mails: chencs@mail.kiz.ac.cn

Kunming Institute of Zoology, CAS