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

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 antiprolifer...

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Main Authors: Arijit Mondal, Tanmoy Guria, Tapan Kumar Maity, Anupam Bishayee
Format: Article
Language:English
Published: MDPI AG 2016-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/17/10/1604
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spelling doaj-c9bf4a21bef7468faeac27d832e855c92020-11-24T21:52:00ZengMDPI AGInternational Journal of Molecular Sciences1422-00672016-09-011710160410.3390/ijms17101604ijms17101604A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer CellsArijit Mondal0Tanmoy Guria1Tapan Kumar Maity2Anupam Bishayee3Department of Pharmaceutical Chemistry, Bengal College of Pharmaceutical Sciences and Research, Durgapur 713 212, West Bengal, IndiaDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, West Bengal, IndiaDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, West Bengal, IndiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL 33169, USAAmaranthus 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.http://www.mdpi.com/1422-0067/17/10/1604Amaranthus spinosusfatty acidhepatocellular carcinomaantiproliferative effectapoptosiscell cycle regulation
collection DOAJ
language English
format Article
sources DOAJ
author Arijit Mondal
Tanmoy Guria
Tapan Kumar Maity
Anupam Bishayee
spellingShingle Arijit Mondal
Tanmoy Guria
Tapan Kumar Maity
Anupam Bishayee
A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells
International Journal of Molecular Sciences
Amaranthus spinosus
fatty acid
hepatocellular carcinoma
antiproliferative effect
apoptosis
cell cycle regulation
author_facet Arijit Mondal
Tanmoy Guria
Tapan Kumar Maity
Anupam Bishayee
author_sort Arijit Mondal
title A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells
title_short A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells
title_full A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells
title_fullStr A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells
title_full_unstemmed A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells
title_sort novel tetraenoic fatty acid isolated from amaranthus spinosus inhibits proliferation and induces apoptosis of human liver cancer cells
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2016-09-01
description 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.
topic Amaranthus spinosus
fatty acid
hepatocellular carcinoma
antiproliferative effect
apoptosis
cell cycle regulation
url http://www.mdpi.com/1422-0067/17/10/1604
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