Ruanjian Sanjie decoction exhibits antitumor activity by inducing cell apoptosis in breast cancer

Abstract

Traditional Chinese medicine, based on theories developed and practiced for >2,000 years, is one of the most common complementary and alternative types of medicine currently used in the treatment of patients with breast cancer. Ruanjian Sanjie (RJSJ) decoction, is composed of four herbs, including Ban xia (Pinellia ternata), Xia ku cao (Prunella vulgaris), Shan ci gu (Cremastra appendiculata) and Hai zao (Sargassum pallidum), and has traditionally been used for softening hard lumps and resolving hard tissue masses. However, the active compounds and mechanisms of action of RJSJ remain unknown. The present study demonstrated the antitumor activity of RJSJ against Ehrlich ascites carcinoma in Swiss albino mice and breast cancer xenografts in nude mice. Notably, RJSJ does not induce body weight loss, immune function toxicity or myelosuppression in mice, indicating that it is safe and well tolerated. In addition, RJSJ shows potent cytotoxicity against breast cancer cells in vitro by the suppression of the anti-apoptotic proteins B-cell lymphoma 2 and survivin, leading to the activation of caspase-3/7 and caspase-9, and the apoptotic cascade. These findings provide a clear rationale to explore the therapeutic strategy of using RJSJ alone or in combination with chemotherapeutic agents for breast cancer patients and the characterization of its active principles.

Ruanjian Sanjie Decoction Induces Apoptosis in Triple-negative Breast Cancer Cells by Downregulating cIAP1/2 and XIAP

“…In previous studies, we obtained the IC 50 values of RJSJ in MDA-MB-231 and MCF-7 cells as 0.578 and 0.635 mg/ml, respectively 13 . We included Cal-51 and SKBR-3 cells in the analysis to further verify the growth-inhibitory effects of RJSJ.…”

“…All herbs in the RJSJ formula were obtained from Tianjin Zhong Xin Pharmaceutical Group Corporation Ltd. (Tianjin, China). RJSJ was prepared as a lyophilized dry powder of hot water extracts as described previously 13 . The composition was as follows: Pinellia ternate (300 g), Prunella vulgaris (300 g), Cremastra appendiculata (200 g), and Sargassum pallidum (200 g).…”

“…The resultant supernatants were lyophilized, weighed, and stored at − 40 °C until use. The lyophilized dry powder was dissolved in RPMI-1640 medium (Invitrogen; Thermo Fisher Scienti c, Inc., Waltham, MA, USA) at the desired concentration and ltered through 0.22-µm sterilization lters before use 13,19 .…”

“…MDA-MB-231, MCF-7, Cal-51, and SKBR-3 cells in the logarithmic growth phase were seeded in 12-well plates at a density of 5 × 10 4 -10 × 10 4 /well. Based on the results of the MTT assay and our previous studies 13 , adherent cells were treated with different concentrations of RJSJ for 48 h. Changes in cellular morphology were monitored using a ZEISS Axio Observer inverted microscope (ZEISS, Germany).…”

“…Our previous study illustrated that RJSJ has de nite anti-tumor effects in vitro and in vivo. Meanwhile, RJSJ is safe and well tolerated in mice 13,14 . Although RJSJ has been demonstrated to have good curative effects against breast cancer, the fundamental molecular mechanisms have not been systematically explored.…”