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 u sed anticancer drug doxorubicin was reported to induce apoptosis of cancer cells. Growth factors such as epidermal growth factor (EGF) and bioactive l ipids such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (SPP) have been shown to enhance viability and to protect cancer cells against a poptosis. In this study, we investigated the effect of PA on MDA-MB-231 cel ls exposed to the anticancer drug doxorubicin. Cell migration toward PA tea s partially inhibited by doxorubicin treatment, and PA moderately diminishe d 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 expos ed to doxorubicin was markedly enhanced by PA treatment. Thus, PA is able t o increase the apoptotic potential of doxorubicin, and may regulate the eff ects of doxorubicin used for chemotherapy.