Synergistic Cytotoxic and Apoptotic Effects of Local Probiotic Lactobacillus Brevis Isolated from Regional Dairy Products in Combination with Tamoxifen

Abstract

Tamoxifen (TAM), the most widely used anti-estrogenic drug, inhibits the progression of breast cancer through competing with estrogen for binding to the estrogen receptor (ER). Tamoxifen has been the first-line adjuvant endocrine therapy in pre- and postmenopausal patients with ER + breast cancer for two decades. However, due to its side effects, interest in using anticancer agents derived from natural foods has increased. It has recently been stated that some probiotics can improve the efficacy of anticancer drugs via synergistic effects. Here, Local Probiotic Lactobacillus Brevis were isolated and characterized from dairy products and its supernatant was prepared. Proliferation of MCF-7, a breast cancer cell line, was investigated after treatment with Lactobacillus Brevis supernatant (LBS) solely, and in combination with Tamoxifen. In Vitro trials were performed to assess the LBS potency. Bax and Bcl-2 mRNA expression levels and apoptotic effects after these treatments were examined by qRT-PCR and flow cytometry, respectively. The results indicated that LBS induces apoptosis in MCF-7 at high concentrations. Transcription of Bcl-2 was reduced but Bax mRNA expression was enhanced. Tamoxifen’s inhibitory effect on the cell growth was synergistically augmented by LBS. In addition, we found that the Bcl-2 mRNA levels in the cells exposed to TAM/LBS were lower than in those treated with TAM alone. Our findings suggest potential role of LB as an adjuvant therapy in cancer treatment and prevention; along with its underlying mechanism