Effect of phosphatidic acid on human breast cancer cells exposed to doxorubicin.

We previously demonstrated that phosphatidic acid (PA) induces chemotactic migration of highly metastatic breast cancer cells MDA-MB-231. The widely used anticancer drug doxorubicin was reported to induce apoptosis of cancer cells. Growth factors such as epidermal growth factor (EGF) and bioactive lipids such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (SPP) have been shown to enhance viability and to protect cancer cells against apoptosis. In this study, we investigated the effect of PA on MDA-MB-231 cells exposed to the anticancer drug doxorubicin. Cell migration toward PA was partially inhibited by doxorubicin treatment, and PA moderately diminished cell cycle arrest of cells exposed to doxorubicin. Although PA itself was not able to induce apoptosis of MDA-MB-231 cells, apoptosis of cells exposed to doxorubicin was markedly enhanced by PA treatment. Thus, PA is able to increase the apoptotic potential of doxorubicin, and may regulate the effects of doxorubicin used for chemotherapy.