title: Growth inhibitory effect of polyunsaturated fatty acids (PUFAs) on colon cancer cells via their growth inhibitory metabolites and fatty acid composition changes.
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.
authors.affiliation: College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, PR China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Haining
authors.initials: H
authors.lastname: Yu
authors.affiliation: College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, PR China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ni
authors.affiliation: College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, PR China.
authors.forename: Shengrong
authors.initials: S
authors.lastname: Shen
authors.affiliation: UND Life Sciences, 2020 S 360th St, #K-202, Federal Way, WA, 98003, United States of America; Department of Medicine and BioScience Research Centre, GVP Hospital, GVP College of Engineering campus, Visakhapatnam-530 048, India.
authors.forename: Undurti N
authors.initials: UN
authors.lastname: Das
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D044045:Lipoxins / Q000096:biosynthesis; D000071876:Prostaglandin-E Synthases
chemical_list: D000964:Antimetabolites, Antineoplastic; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D054834:Lipocalins; D044045:Lipoxins; C040527:lipoxin A4; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C583212:ALOX5 protein, human; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D005472:Fluorouracil