Differential effects of saturated and unsaturated fatty acids on ovarian cancer growth.
Uddin MH, Buekers TE, Elshaikh MA, Giri S, Munkarah AR, and Rattan R. Differential effects of saturated and unsaturated fatty acids on ovarian cancer growth. Gynecologic Oncology 2017; 145:210.
Objective: Free fatty acids (FFAs) acquired from the omentum have been demonstrated to promote epithelial ovarian cancer growth (EOC). Different FFAs (saturated or unsaturated) are involved in different physiological functions. The present study was designed to investigate and compare the effects of oleate, the most abundant circulating unsaturated FFA, to those of the saturated FFA palmitate in established human ovarian cancer cell lines. Method: Ovarian cancer cell lines (A2780, OVCAR5, CaOV3, and ID8) were exposed to various concentrations of either oleate (C:18:1) or palmitate (C:16) after overnight serum starvation. Proliferation and survival were measured over 72 hours by Promega proliferation assay and MTT. Apoptosis was measured by caspase 3 activity (Promega). Expression of free fatty acid receptor (FFAR) 1 and 4 was measured after exposure to oleate and palmitate by quantitative polymerase chain reaction. Results: The unsaturated FA oleate stimulated cell proliferation in a time-and dose-dependent manner (P ranges from 0.05 to 0.01 for various cells and time points) in the 4 ovarian cell lines. On the contrary, palmitate caused apoptotic cell death in all 4 ovarian cancer cell lines in a time-and dose-dependent manner (P ranges from 0.05 to 0.001 for various cells and time points). Interestingly, when all 4 cell lines were exposed to a combination of both FAs, the final effect was increased cell proliferation; in fact, oleate seemed to protect the cancer cells against the apoptotic action of palmitate in a dosedependent manner. Blocking of FFAR1 reversed the proliferative effect of oleate in ovarian cancer cells (P b 0.05-0.001). Oleate induced the pro-oncogenic signaling of AKT, while palmitate inhibited it. Conclusion: Different fatty acids have distinct effect on ovarian cancer cell proliferation and apoptosis. While the unsaturated FFA oleate promotes proliferation likely by activating Akt, the saturated FFA palmitate appears to cause apoptosis and inhibits Akt. The type of FFA and their ratios in the tumor environment may influence ovarian cancer growth and progression. This will be further investigated in vivo and patient-derived specimens.