Oleate activates phosphatidylinositol 3-kinase and promotes proliferation and reduces apoptosis of MDA-MB-231 breast cancer cells, whereas palmitate has opposite effects - PubMed (original) (raw)

. 2000 Nov 15;60(22):6353-8.

Affiliations

PMID: 11103797

Oleate activates phosphatidylinositol 3-kinase and promotes proliferation and reduces apoptosis of MDA-MB-231 breast cancer cells, whereas palmitate has opposite effects

S Hardy et al. Cancer Res. 2000.

Abstract

Epidemiological studies and experiments using animal models and cultured breast cancer cells have suggested that a high intake of dietary fat could increase breast cancer risk. Little is known about the biochemical pathways by which various free fatty acids (FFAs) influence breast cancer cell proliferation and apoptosis. The present study was designed to investigate the effects of the two most abundant circulating FFAs, oleate and palmitate, on established human breast cancer cell lines after a short period of serum starvation. The unsaturated FFA oleate (C🔞1) stimulated cell proliferation, whereas the saturated FFA palmitate (C:16) dose dependently inhibited it. The half maximal effective concentrations of oleate and palmitate in the presence of albumin were 5 and 25 microM, respectively. The growth-inhibitory effect of palmitate in MDA-MB-231 cells was related to the induction of apoptosis as indicated by morphological and biochemical criteria. Moreover, oleate protected cells against the proapoptotic action of palmitate. Oleate and palmitate increased and decreased phophatidylinositol 3-kinase (PI3-K) activity, respectively, and the actions of the two FFAs on the enzyme were antagonistic. The PI3-K inhibitors wortmannin and LY294002 completely blocked the proliferative action of oleate. 2-Bromopalmitate, a nonmetabolizable analogue, did not affect MDA-MB-231 cell proliferation, suggesting that palmitate must be metabolized to exert its effect. Thus, various types of fatty acids are not equivalent with respect to their actions on breast cancer cell proliferation and apoptosis. The results support the concept that PI3-K is implicated in the control of breast cancer cell growth by FFAs and that PI3-K may provide a link between fat and cancer. The data are also consistent with the view that the type of FFA and their ratios in the diet in addition to the total amount of fat influence mammary carcinogenesis.

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Oleate activates phosphatidylinositol 3-kinase and promotes proliferation and reduces apoptosis of MDA-MB-231 breast cancer cells, whereas palmitate has opposite effects - PubMed (original) (raw)