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Int. J. Mol. Sci. 2016, 17(10), 1604; doi:10.3390/ijms17101604

A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells

1
Department of Pharmaceutical Chemistry, Bengal College of Pharmaceutical Sciences and Research, Durgapur 713 212, West Bengal, India
2
Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, West Bengal, India
3
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL 33169, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Maurizio Battino
Received: 9 May 2016 / Revised: 9 September 2016 / Accepted: 12 September 2016 / Published: 22 September 2016
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention)
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Abstract

Amaranthus spinosus Linn. (Family: Amaranthaceae) has been shown to be useful in preventing and mitigating adverse pathophysiological conditions and complex diseases. However, only limited information is available on the anticancer potential of this plant. In this study, we examined the antiproliferative and pro-apoptotic effects of a novel fatty acid isolated from A. spinosus—(14E,18E,22E,26E)-methyl nonacosa-14,18,22,26 tetraenoate—against HepG2 human liver cancer cells. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine cell viability, flow cytometry assay for cell cycle analysis, and Western blot analysis to measure protein expression of Cdc2), cyclin B1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2). The MTT assay showed that the fatty acid markedly inhibited the proliferation of HepG2 cells in a dosage-dependent fashion, with a half maximal inhibitory concentration (IC50) value of 25.52 µmol/L. This antiproliferative result was superior to that of another known fatty acid, linoleic acid (IC50 38.65 µmol/L), but comparable to that of standard anticancer drug doxorubicin (IC50 24.68 µmol/L). The novel fatty acid also induced apoptosis mediated by downregulation of cyclin B1, upregulation of Bax, and downregulation of Bcl-2, resulting in the G2/M transition arrest. Our results provide the first experimental evidence that a novel fatty acid isolated from A. spinosus exhibits significant antiproliferative activity mediated through the induction of apoptosis in HepG2 cells. These encouraging results may facilitate the development of A. spinosus fatty acid for the prevention and intervention of hepatocellular carcinoma. View Full-Text
Keywords: Amaranthus spinosus; fatty acid; hepatocellular carcinoma; antiproliferative effect; apoptosis; cell cycle regulation Amaranthus spinosus; fatty acid; hepatocellular carcinoma; antiproliferative effect; apoptosis; cell cycle regulation
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Mondal, A.; Guria, T.; Maity, T.K.; Bishayee, A. A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells. Int. J. Mol. Sci. 2016, 17, 1604.

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