The Indole-3-carbinol Cyclic Tetrameric Derivative CTet Synergizes with Cisplatin and Doxorubicin in Triple-negative Breast Cancer Cell Lines

The indole-3-carbinol cyclic tetrameric derivative (CTet) inhibits breast cancer cell proliferation by endoplasmic reticulum stress and autophagyrelated cell death induction, AKT/PKB (protein kinase B) activity inhibition and p53-independent overexpression of cyclin-dependent kinase inhibitor-1A (p21/CDKN1A). In the present study we evaluated the synergistic activity of CTet in combination with cisplatin and doxorubicin in triple-negative breast cancer cell lines. Materials and Methods: Synergisms were evaluated in terms of cell viability, induction of autophagy and overexpression of microtubule-associated protein-1 light chain-3 beta (MAP1LC3B) autophagy-related gene in MDA-MB-231 and BT-20 triple-negative breastcancer cells. Results: We demonstrated that CTet in combination with both cisplatin and doxorubicin synergistically inhibits cell viability and induces autophay. The MAP1LC3B gene was synergistically overexpressed in MDA-MB-231 cells treated with CTet-cisplatin combination. Moreover, the cytotoxic activity of CTet was improved in cells pre-treated with cisplatin and doxorubicin. Conclusion: This preliminary in vitro study confirms the potential of CTet as a chemopreventive agent or chemotherapeutic in combination with standard approaches for triple-negative breast cancer