Linoleic acid suppresses colorectal cancer cell growth by inducing oxidant stress and mitochondrial dysfunction

Abstract

Some polyunsaturated fatty acids (PUFAs), if not all, have been shown to have tumoricidal action, but their exact mechanism(s) of action is not clear. In the present study, we observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at high concentrations (above 300 μM); while low concentrations (100-200 μM) promoted proliferation. Analysis of cell mitochondrial membrane potential, reactive oxygen species (ROS) formation, malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) activity suggested that anti-cancer action of LA is due to enhanced ROS generation and decreased cell anti-oxidant capacity that resulted in mitochondrial damage. Of the three cell lines tested, semi-differentiated colorectal cancer cells RKO were most sensitive to the cytotoxic action of LA, followed by undifferentiated colorectal cancer cell line (LOVO) while the normal human umbilical vein endothelial cells (HUVEC) were the most resistant (the degree of sensitivity to LA is as follows: RKO > LOVO > HUVEC). LA induced cell death was primed by mitochondrial apoptotic pathway. Pre-incubation of cancer cells with 100 μM LA for 24 hr enhanced sensitivity of differentiated and semi-differentiated cells to the subsequent exposure to LA. The relative resistance of LOVO cells to the cytotoxic action of LA is due to a reduction in the activation of caspase-3. Thus, LA induced cancer cell apoptosis by enhancing cellular oxidant status and inducing mitochondrial dysfunction.

Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines

“…18 As shown in Fig. 2 and Table 1, addition of u-3 PUFAs, especially DHA, increased production of peroxides and MDA in LS174T and to a lesser extent in HT29 cells.…”

β-Lactoglobulin-linoleate complexes: In vitro digestion and the role of protein in fatty acid uptake

“…As linoleate has to be transported into the cell to be cytotoxic (Lu et al, 2010), this would infer that a portion of the linoleate remains bound to the protein or peptides after in vitro gastro-duodenal digestion. Even if it is assumed that linoleate dissociates from the protein under gastric conditions (pH 2.5), complexes could reform under duodenal digestion conditions (pH 6.5) (Ragona et al, 2000) The interaction between FA and βlg is pHdependent: at low pH (below pH 6), FA are released from the βlg but the interaction is reversible when the pH is increased.…”

Evaluation of Colorectal Cancer (CRC) Epidemiology A Pharmacogenomic Approach

“…The reported compounds induce apoptosis in carcinoma cells by increased production of 'Reactive Oxygen Species (ROS)' , leading into environmental stress and ultimately causing cell death. 23 Oleic acid suppresses the over expression of HER2 gene, which helps in invasive progression and metastasis in human cancer. 24 Fish oil and olive oil decrease the proliferation and early down regulation of COX2 followed by reduced BCL2 expression.…”