Effect of essential fatty acids (EFAs) and their metabolites on the growth suppressive action of anti-cancer drug doxorubicin on neuro- and glioblastoma cells in vitro.

Cancer of neural cell origin are one of the most difficult to treat given their high resistance to chemotherapeutic drugs and high rate of recurrence. Furthermore, chemotherapy and radiotherapy interfere with the proliferation and survival of normal cells and thus, cause serious side effects. Essential fatty acids (EFAs) and their metabolites have been shown to induce apoptosis of tumor cells with no effect on normal cells. In the present study, we evaluated the effect of EFAs and their metabolites in combination of with anticancer drug doxorubicin on the proliferation, survival and potential mechanisms(s) of EFAs and their metabolites on three different tumor cells: human neuroblastoma cells (IMR-32) and human glioma cells (HNGC2 and LN229) in vitro. Of all the lipids tested, AA (arachidonic acid) and EPA (eicosapentaenoic acid) were found to be the most potent in their anti-tumor activity on both neuroblastoma and glioma cells in vitro. Both AA and EPA augmented the anti-tumor action of doxorubicin (IMR-32 > HNGC2 + LN229). Oxidative stress seems to have a major role in the induction of apoptosis of neuroblastoma cells (IMR-32) whereas, glioma cells (HNGC2 and LN229) showed activation of intrinsic apoptotic pathway leading to their death.