Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro

Sailaja Polavarapu, Arul M. Mani, Naveen K.V. Gundala, Anasuya D. Hari, Siresha Bathina, Undurti N. Das, Daotai Nie

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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 x 104 cells/100 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 (PGE1t PGE2, PGF2a, and PGI2) and leukotrienes (LTD4 and LTE4) tested; PGE-i, 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 (.ig/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.

Original languageEnglish (US)
Article numbere114766
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 23 2014

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Bleomycin
Metabolites
Unsaturated Fatty Acids
Neuroblastoma
polyunsaturated fatty acids
metabolites
Growth
CD59 Antigens
Leukotriene D4
cells
peroxides
Lipid Peroxides
oxidants
Dinoprostone
Oxidants
nordihydroguaiaretic acid
Lipoxins
leukotrienes
Leukotriene E4
Masoprocol

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro. / Polavarapu, Sailaja; Mani, Arul M.; Gundala, Naveen K.V.; Hari, Anasuya D.; Bathina, Siresha; Das, Undurti N.; Nie, Daotai.

In: PLoS One, Vol. 9, No. 12, e114766, 23.12.2014.

Research output: Contribution to journalArticle

Polavarapu, Sailaja ; Mani, Arul M. ; Gundala, Naveen K.V. ; Hari, Anasuya D. ; Bathina, Siresha ; Das, Undurti N. ; Nie, Daotai. / Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro. In: PLoS One. 2014 ; Vol. 9, No. 12.
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AU - Hari, Anasuya D.

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AU - Das, Undurti N.

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