The Ethyl Acetate Fraction of Marine Sponge Stylissa carteri Induces Breast Cancer Cell Death via Upregulation of Mcl-1S: an In vitro Study

OBJECTIVE: To evaluate the potency of the fraction of marine sponge Stylissa carteri in inducing cell death, inhibiting spheroid growth, and its impact on pro-apoptotic protein Mcl-1S in breast cancer cells. METHODS: Stylissa carteri were collected from Pramuka Island followed by ethanol extraction and ethyl acetate fractionation. To evaluate the cytotoxic effect of fraction, the HCC-1954, MDA MB 231, and MCF-7 cells were treated with the fraction of Stylissa carteri and MTT assay was then performed. The effect on spheroid growth was evaluated in HCC-1954 cells. The combined effect of the ethyl acetate fraction and paclitaxel were analyzed using combination index (CI) and immunoblotting on the pro-apoptotic protein Mcl-1S. Furthermore, compounds in this fraction were identified using GC-MS. RESULTS: Data showed that both the MDA MB 231 and HCC-1954 cells were interestingly more sensitive to the fraction as compared with MCF-7 cells. The IC(50) of the ethyl acetate fraction on HCC-1954, MDA MB 231 and MCF-7 were 4.1 µg/ml, 3.9 µg/ml, and 123.8 µg/ml, respectively. In addition, the fraction triggered spheroid destruction within 10 days. The CI of paclitaxel and ethyl acetate fraction of Stylissa carteri were less than 0.52. Moreover, this combination induced upregulation of the Mcl-1S protein. Furthermore, some fatty acid-based structures were predicted as the major compounds in this fraction. CONCLUSION: The ethyl acetate fraction of Stylissa carteri induces cell death and spheroid destruction in aggressive breast cancer cells. It has a synergistic cytotoxic effect with paclitaxel on MDA MB 231 cell death and upregulates Mcl-1S protein.