Iturin A and Gramicidin A inhibit proliferation, trigger apoptosis, and regulate inflammation in breast cancer cells

Altın-Çelik P., Eken A., Derya Andeden M., Eciroğlu H., Uzen R., Altuntaş H.

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.100, ss.1-14, 2024 (SCI-Expanded)

Özet

Biosurfactants with antibiotic, antiviral, anti-tumor, and immunomodulatory properties appear to have potential in cancer treatment due to their lack of known toxicities compared with conventional chemotherapy. However, there are few studies on the use of biosurfactants for the treatment of breast cancer. In this study, to develop a new strategy for breast cancer treatment, we evaluated the anti-proliferative, anti-inflammatory, anti-tumor, and apoptotic effects of two different biosurfactants (Iturin A and Gramicidin A) from bacillus in both single and binary combination on two breast cancer cell lines (MDA-MB-231 and MCF-7, which is estrogen receptornegative and positive, respectively). First, the anti-proliferative effects of Iturin A and Gramicidin A, both single and in combination, were explored by MTT assay. Then, the effects of Iturin A and Gramicidin A on inflammatory factors were evaluated using the ELISA method. Apoptosis was assessed using Annexin V-PE/7-AAD and Giemsa staining methods. RT-qPCR analysis was used to evaluate the expressions of several cytokines with anti-tumor and apoptotic properties and the apoptotic BAX and BCL2 genes. Biosurfactants showed antiproliferative and anti-tumor properties by decreasing the viability of MDA-MB-231 and MCF-7 cells depending on concentration and time (p < 0.05-p<0.01). Biosurfactants induced apoptosis by stimulating apoptotic cell death (p < 0.05-p<0.001) and by increasing BAX and decreasing BCL2 gene expression levels (p < 0.05- p<0.001) in breast cancer cells. Biosurfactants also regulated the expressions of extracellular and intracellular cytokines (IL-2, IL-6, IL-12, IL12RB2, TGFβ, TNFα, VEGF) and chemokines (IL-8, CCL2, CXCL10) in breast cancer cells (p < 0.05-p<0.01). Both single and binary combination applications of Iturin A and Gramicidin A biosurfactants, may potentially treat breast cancer patients, and the in vitro results presented here warrant further in vivo studies.