Evaluating the antitumor activity of sphingosine-1-phosphate against human triple-negative breast cancer cells with basal-like morphology.
Omar AbuhusseinJian YangPublished in: Investigational new drugs (2020)
Sphingosine-1-phosphate (S1P) is an important sphingolipid metabolite that regulates a wide range of physiological and pathophysiological processes. Our previous studies show that S1P selectively induces cell apoptosis in human breast cancer luminal A subtype cell line MCF7. In addition, S1P exhibits synergistic effects with chemotherapy drugs against both MCF7 and luminal B subtype cell line MDA-MB-361 at concentration in the high nM to low μM range. In the current study, we evaluated the effect of S1P on proliferation, apoptosis and cytotoxicity towards a panel of nine triple-negative breast cancer with basal-like morphology (TNBC-BL) cell lines (HCC1599, HCC1937, HCC1143, MDA-MB-468, HCC38, HCC70, HCC1806, HCC1187 and DU4475) in the same concentration range. S1P exhibited mild to moderate effects (<20% increase comparted to control) towards the TNBC-BL cell lines except HCC38, HCC70 and HCC1806. Furthermore, it increased cell apoptosis by ~15-20% in all the cell lines compared to the control, and elicited moderate to strong cytotoxic effect towards all cell lines except MDA-MB-468 and HCC1806. However, no synergistic/additive effect was observed between S1P and chemotherapy drug docetaxel for any TNBC-BL cell line.