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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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Changes in the fatty acid compositions of LoVo cells that were supplemented for 48 hours with various PUFAs and 5-FU.
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pone.0123256.g003: Changes in the fatty acid compositions of LoVo cells that were supplemented for 48 hours with various PUFAs and 5-FU.

Mentions: In the present study, we analyzed fatty acid composition of LoVo and RKO cells in response to supplementation with various PUFAs and 5-FU for 48h and are shown in Table 1 and Figs 3 and 4. 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 also calculated. These results indicated that when supplemented with PUFAs, fatty acid profiles of LoVo and RKO cells were significantly different compared with control group. As shown in Table 1, it is noteworthy that levels of supplemented fatty acids were significantly increased in LoVo and RKO cells. For instance, LoVo cells supplemented with ALA, DHA, EPA, LA, AA, GLA showed a 54.9-fold, 12.32-fold, 16.6-fold, 13.95-fold, 3.17-fold and 39.88-fold higher concentrations respectively compared to the control. On the other hand, RKO cells treated with ALA, DHA, EPA, LA, AA, GLA showed a 14.09-fold, 54.81-fold, 225.95-fold, 31.71-fold, 44.46-fold and 18.41-fold increase in the concentrations of these fatty acids respectively. It is noteworthy that both in LoVo and RKO cells showed a substantial increase in EPA and DHA levels when supplemented with EPA suggesting that EPA is converted to its long-chain metabolite DHA. In addition, supplementation of AA enhanced the content of AA and EPA in both LoVo and RKO cells. Surprisingly, LoVo cells supplemented with GLA resulted in not only a significant increase in their GLA content but also an increase in ALA, EPA, DHA, LA and AA. In contrast, RKO cells supplemented with GLA showed a decrease in ALA, EPA, DHA and LA content in comparison to control.


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)

Changes in the fatty acid compositions of LoVo cells that were supplemented for 48 hours with various PUFAs and 5-FU.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123256.g003: Changes in the fatty acid compositions of LoVo cells that were supplemented for 48 hours with various PUFAs and 5-FU.
Mentions: In the present study, we analyzed fatty acid composition of LoVo and RKO cells in response to supplementation with various PUFAs and 5-FU for 48h and are shown in Table 1 and Figs 3 and 4. 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 also calculated. These results indicated that when supplemented with PUFAs, fatty acid profiles of LoVo and RKO cells were significantly different compared with control group. As shown in Table 1, it is noteworthy that levels of supplemented fatty acids were significantly increased in LoVo and RKO cells. For instance, LoVo cells supplemented with ALA, DHA, EPA, LA, AA, GLA showed a 54.9-fold, 12.32-fold, 16.6-fold, 13.95-fold, 3.17-fold and 39.88-fold higher concentrations respectively compared to the control. On the other hand, RKO cells treated with ALA, DHA, EPA, LA, AA, GLA showed a 14.09-fold, 54.81-fold, 225.95-fold, 31.71-fold, 44.46-fold and 18.41-fold increase in the concentrations of these fatty acids respectively. It is noteworthy that both in LoVo and RKO cells showed a substantial increase in EPA and DHA levels when supplemented with EPA suggesting that EPA is converted to its long-chain metabolite DHA. In addition, supplementation of AA enhanced the content of AA and EPA in both LoVo and RKO cells. Surprisingly, LoVo cells supplemented with GLA resulted in not only a significant increase in their GLA content but also an increase in ALA, EPA, DHA, LA and AA. In contrast, RKO cells supplemented with GLA showed a decrease in ALA, EPA, DHA and LA content in comparison to control.

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