title: Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro.
abstract: In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs) tested on human neuroblastoma IMR-32 (0.5 × 10(4) cells/100 µl of IMR) cells (EPA > DHA > ALA = GLA = AA > DGLA = LA: ∼ 60, 40, 30, 10-20% respectively) at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2α, and PGI2) and leukotrienes (LTD4 and LTE4) tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4), 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA) and 10(S),17(S)-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S),17(S)DiHDoHE), metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA) at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions.
authors.affiliation: Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering Campus, Madhurawada, Visakhapatnam-530048, Andhra Pradesh, India.
authors.forename: Sailaja
authors.initials: S
authors.lastname: Polavarapu
authors.affiliation: Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering Campus, Madhurawada, Visakhapatnam-530048, Andhra Pradesh, India.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Mani
authors.affiliation: Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering Campus, Madhurawada, Visakhapatnam-530048, Andhra Pradesh, India.
authors.forename: Naveen K V
authors.initials: NK
authors.lastname: Gundala
authors.affiliation: Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering Campus, Madhurawada, Visakhapatnam-530048, Andhra Pradesh, India.
authors.forename: Anasuya D
authors.initials: AD
authors.lastname: Hari
authors.affiliation: Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering Campus, Madhurawada, Visakhapatnam-530048, Andhra Pradesh, India.
authors.forename: Siresha
authors.initials: S
authors.lastname: Bathina
authors.affiliation: UND Life Sciences, 2020 S 360th St, # K-202, Federal Way, Washington, 98003, United States of America.
authors.forename: Undurti N
authors.initials: UN
authors.lastname: Das
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001761:Bleomycin / Q000633:toxicity*; D018957:CD59 Antigens / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002457:Cell Extracts; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D015289:Leukotrienes / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D044045:Lipoxins / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009447:Neuroblastoma / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000975:Antioxidants; D018957:CD59 Antigens; D002457:Cell Extracts; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D015289:Leukotrienes; D044045:Lipoxins; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; C040527:lipoxin A4; D001761:Bleomycin; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D009569:Nitric Oxide