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Growth inhibitory effect of polyunsaturated fatty acids (PUFAs) on colon cancer cells via their growth inhibitory metabolites and fatty acid composition changes.

Zhang C, Yu H, Ni X, Shen S, Das UN - PLoS ONE (2015)

Bottom Line: PUFAs 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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, PR China.

ABSTRACT

Background: Colorectal 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.

Methods: Human 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.

Results: PUFAs 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.

Conclusions: Tumoricidal 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.

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Related in: MedlinePlus

Effect of ALA, DHA, EPA, LA, AA, GLA and 5-FU on the expression of COX-2 and ALOX5 in RKO cells by ELISA.Values in the same column with different letters are significantly different (p<0.05).
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pone.0123256.g008: Effect of ALA, DHA, EPA, LA, AA, GLA and 5-FU on the expression of COX-2 and ALOX5 in RKO cells by ELISA.Values in the same column with different letters are significantly different (p<0.05).

Mentions: COX-2 plays an important role in both inflammation and colon carcinogenesis and hence, it has been suggested that agents that suppress its expression may be useful in inhibiting these two processes [24]. On the other hand, growing body of evidence indicates that arachidonate 5-lipoxygenase (ALOX5) is a crucial regulator of inflammation and cancer pathogenesis [25]. In the present study, we measured the expression of COX-2 following supplementation of PUFAs and 5-FU, which showed that, in general, PUFAs (except for AA on LoVo and GLA and AA on RKO cells) down-regulated the expression of COX-2 compared to control as is evident from the results shown in Figs 6 and 7, while PUFAs (except for EPA on RKO cells) down-regulated the expression of ALOX5 compared to control as seen from the results depicted in Figs 7 and 8. On the other hand, 5-FU inhibited the expression of COX-2 and ALOX5 in LoVo cells but enhanced in RKO cells.


Growth inhibitory effect of polyunsaturated fatty acids (PUFAs) on colon cancer cells via their growth inhibitory metabolites and fatty acid composition changes.

Zhang C, Yu H, Ni X, Shen S, Das UN - PLoS ONE (2015)

Effect of ALA, DHA, EPA, LA, AA, GLA and 5-FU on the expression of COX-2 and ALOX5 in RKO cells by ELISA.Values in the same column with different letters are significantly different (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401647&req=5

pone.0123256.g008: Effect of ALA, DHA, EPA, LA, AA, GLA and 5-FU on the expression of COX-2 and ALOX5 in RKO cells by ELISA.Values in the same column with different letters are significantly different (p<0.05).
Mentions: COX-2 plays an important role in both inflammation and colon carcinogenesis and hence, it has been suggested that agents that suppress its expression may be useful in inhibiting these two processes [24]. On the other hand, growing body of evidence indicates that arachidonate 5-lipoxygenase (ALOX5) is a crucial regulator of inflammation and cancer pathogenesis [25]. In the present study, we measured the expression of COX-2 following supplementation of PUFAs and 5-FU, which showed that, in general, PUFAs (except for AA on LoVo and GLA and AA on RKO cells) down-regulated the expression of COX-2 compared to control as is evident from the results shown in Figs 6 and 7, while PUFAs (except for EPA on RKO cells) down-regulated the expression of ALOX5 compared to control as seen from the results depicted in Figs 7 and 8. On the other hand, 5-FU inhibited the expression of COX-2 and ALOX5 in LoVo cells but enhanced in RKO cells.

Bottom Line: PUFAs 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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, PR China.

ABSTRACT

Background: Colorectal 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.

Methods: Human 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.

Results: PUFAs 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.

Conclusions: Tumoricidal 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.

Show MeSH
Related in: MedlinePlus