CAL-148

Xiaochaihu Decoction Inhibits the Proliferation of Breast Cancer Cells In Vitro

Xiaochaihu (XCH) decoction is a traditional Chinese prescription that has been recorded in the pharmacopeia of the People's Republic of China. In China, the XCH decoction is used clinically to treat a variety of tumors, including breast cancer. However, its potential mechanism of action is still undefined.

To confirm the inhibitory effect of the XCH decoction on breast tumor cells, different concentrations of the XCH decoction (0, 2.5, 5, 10, 20, 40, 80 or 160 μg/mL) were used to treat different breast cancer cell lines. After 48 hours, cell viability was determined by a CCK-8 assay. The results showed that the XCH decoction inhibited the proliferation of breast cancer cells, especially CAL-148 and MCF-7 cells (Fig. 1A). Subsequently, to further verify the effectiveness of the XCH decoction, CAL-148 and MCF-7 cells were treated with different concentrations of the XCH decoction for 24 h, 48 h or 72 h. The data demonstrated that the XCH decoction significantly curbed the growth of CAL-148 and MCF-7 cells in a dose- and time-dependent manner (Fig. 1B, 1C). In addition, after treatment with the XCH decoction for 48 hours, cell survival decreased, as determined by 40-fold light microscopy (Fig. 1D). A colony formation assay was used to evaluate the effect of the XCH decoction on proliferation, and the results showed that the number of cell clones in the XCH decoction group was dramatically less than that in the control group (Fig. 1E, 1F).

Fig. 1. Xiaochaihu decoction restrains breast cancer cell proliferation in vitro (Liu, Qinglong, et al. 2024).

Synergistic Effect of Chidamide Combined with Enzalutamide In Vitro

In this study, we chose chidamide, a selective histone deacetylase (HDAC) inhibitor targeting HDAC 1/2/3/10 subtypes. As a candidate drug compatible with the anti-androgen receptor (AR) agent enzalutamide, for the treatment of luminal androgen receptor (LAR) subtype of triple-negative breast cancer (TNBC). It is worth noting that chemotherapy is the main strategy for TNBC, and LAR TNBCs are characterized by a high frequency of PI3K mutations. Therefore, we selected the PI3Ki alpelisib and paclitaxel as controls.

We conducted growth inhibition assays to investigate the drug sensitivity of MDA-MB-453 and CAL-148 cell lines, both categorized as the LAR subtype. Our findings indicate that MDA-MB-453 cells were significantly inhibited by chidamide and showed overall sensitivity to all tested drugs (Fig. 2A). CAL-148 cells exhibited increased sensitivity to chidamide, paclitaxel, and alpelisib but demonstrated resistance to enzalutamide (Fig. 2B). This study confirmed that the combination of HDAC inhibitors and AR antagonists possessed greater therapeutic efficacy than monotherapy in LAR TNBC.

Fig. 2. Cell viability of MDA-MB-453 and CAL-148 cell lines treated with chidamide or enzalutamide (Zhao, Ya-Xin, et al. 2024).