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 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.
Department of Pharmaceutical Chemistry, Bengal College of Pharmaceutical Sciences and Research, Durgapur 713 212, West Bengal, India. arijit_ncp@rediffmail.com.
Arijit
A
Mondal
Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, West Bengal, India. tguria.ju@gmail.com.
Tanmoy
T
Guria
Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, West Bengal, India. jutkmaity@yahoo.com.
Tapan Kumar
TK
Maity
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL 33169, USA. abishayee@ularkin.org.
Anupam
A
Bishayee
D027721:Amaranthus / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D056744:Cyclin B1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C000602013:(14E,18E,22E,26E)-methyl nonacosa-14,18,22,26 tetraenoate; D000970:Antineoplastic Agents; D056744:Cyclin B1; D005231:Fatty Acids, Unsaturated; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
Amaranthus spinosus; antiproliferative effect; apoptosis; cell cycle regulation; fatty acid; hepatocellular carcinoma
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