MSBA-S - A pentacyclic sulfamate as a new option for radiotherapy of human breast cancer cells

Abstract

Many pentacyclic triterpenoids show anti-cancer and anti-inflammatory properties. Recently, we detected a pronounced cytotoxicity and radiosensitivity of two betulinyl sulfamates in human breast cancer cells. Besides betulinic acid scaffold (BSBA-S), we synthesized several new sulfamate-coupled scaffolds from oleanolic acid (OSBA-S), ursolic acid (USBA-S), platanic acid (PSBA-S) and maslinic acid (MSBA-S). Highest cytotoxicity was monitored in breast cancer cell lines after MSBA-S treatment showing in SRB assays IC₅₀ values between 3.7 μM and 5.8 μM. Other sulfamate/triterpene conjugates, however, were less cytotoxic holding IC₅₀ values between 6.6 μM and >50 µM, respectively. MSBA-S-treated breast cancer cells displayed significantly reduced clonogenic survival and an increased rate of apoptosis as compared to the other conjugates. In addition, MSBA-S in combination with irradiation resulted in effects on radiosensitivity in MDA-MB-231 cells (DMF₁₀ = 1.14). In particular, ROS formation was strongly assessed in MSBA-S-treated breast cancer cells. Our findings suggest that the sulfamate derivative of maslinic acid MSBA-S might be a new option for the radiation therapy in breast cancer cells.

Keywords: Apoptosis; Cytotoxicity; Pentacyclic triterpenoic acid; Radiotherapy; Sulfamates; Triple negative human breast cancer.