Abstract
BackgroundColorectal cancer is common. Polyunsaturated fatty acids (PUFAs) exert growth-inhibitory and pro-apoptotic effects on colon cancer cells. Metabolites of PUFAs such as prostaglandins (PGs), leukotrienes (LTs) and lipoxins (LXs) play a significant role in colon cancer.MethodsHuman colon cancer LoVo and RKO cells were cultured with different concentration of PUFAs and 5-fluorouracil (5-FU) in vitro. Cell morphological changes, fatty acid composition, formation of PGE2, LTB4 and LXA4 and expression of COX-2, ALOX5, PGD synthase (PGDS), microsomal prostaglandin E synthase (mPGES) were assessed in LoVo and RKO cells when supplemented with PUFAs and 5-FU.ResultsPUFAs and 5-FU inhibited growth of LoVo and RKO cells to the same extent at the doses used and produced significant alterations in their shape. As expected, higher concentrations of supplemented PUFAs were noted in the cells compared to control. LA, GLA, AA, ALA and EPA supplementation to LoVo cells suppressed production of PGE2, LTB4,and ALOX5, mPGES expression, but enhanced that of LXA4; whereas DHA enhanced PGE2 and LXA4 synthesis but decreased LTB4 formation and COX-2, ALOX5, mPGES expression. In contrast, 5-FU enhanced formation of PGE2, LTB4 and mPGES expression, but suppressed LXA4 synthesis and COX-2 expression. PGE2, LTB4 synthesis and ALOX5 expression was suppressed by LA, GLA, ALA and DHA; whereas AA, EPA and 5-FU enhanced PGE2 but paradoxically AA decreased and EPA and 5-FU enhanced LTB4 synthesis in RKO cells. All the PUFAs tested enhanced, while 5-FU decreased LXA4 formation in RKO cells; whereas GLA, AA, and 5-FU augmented while LA, ALA, EPA and DHA enhanced COX-2 expression in RKO cells.ConclusionsTumoricidal action of PUFAs on colorectal LoVo and RKO cancer cells in vitro was associated with increased formation of LXA4, decreased synthesis of PGE2 and LTB4 and suppressed expression of COX-2, ALOX5, mPGES, whereas 5-FU produced contrasting actions on these indices.
Highlights
Colorectal cancer is common both in males and females, with the highest incidence in Australia and New Zealand, Europe, and North America [1]
Fatty acid composition, formation of PGE2, LTB4 and LXA4 and expression of COX-2, ALOX5, PGD synthase (PGDS), microsomal prostaglandin E synthase were assessed in LoVo and RKO cells when supplemented with Polyunsaturated fatty acids (PUFAs) and 5-FU
The ratio of unsaturated fatty acids/saturated fatty acids (S/U) and the ratio of n-6 PUFAs/n-3 PUFAs (n-6/n-3) were calculated. These results indicated that when supplemented with PUFAs, fatty acid profiles of LoVo and RKO cells were significantly different compared with control group
Summary
Colorectal cancer is common both in males and females, with the highest incidence in Australia and New Zealand, Europe, and North America [1]. Overexpression of cyclooxygenase-2 (COX-2), which leads to the formation of excess of PGE2, has been associated with pro-inflammatory events and higher incidence of colorectal cancer [14,15,16]. These evidences indicate that COX-2 is a potential target for anti-cancer treatment. This is supported by the observation that n-3 PUFAs: DHA and EPA in combination with radiotherapy suppressed the growth of HT29 colon cancer cells that was associated with decreased COX-2 expression [17]. Metabolites of PUFAs such as prostaglandins (PGs), leukotrienes (LTs) and lipoxins (LXs) play a significant role in colon cancer
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