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.
Highlights
Cancer has become an enormous global health burden, because there are approximately 12.7 million cancer cases and 7.6 million cancer deaths every year [1,2]
Our results showed that the fatty acid induced significant cell cycle alteration and arrested cancer cells at the G0/G1 interface, which indicates the antiproliferative potency of the A. spinosus fatty acid
The results of our present investigation clearly indicate that a novel fatty acid from A. spinosus is a potent growth inhibitor of cultured HepG2 cancer cells
Summary
Cancer has become an enormous global health burden, because there are approximately 12.7 million cancer cases and 7.6 million cancer deaths every year [1,2]. Hepatocellular carcinoma (HCC), the most predominant pattern of liver cancer, is the sixth most common cancer and the third leading cause of cancer mortality worldwide [3]. The incidence of HCC in the United States has dramatically increased by more than 70% in the past 25 years [4]. 2016, 17, 1604 in the United States has dramatically increased by more than 70% in the past 25 years [4]. According to the American Cancer Society, an estimated 35,660 new instances of liver cancer (including tihnetrAahmeepraictiacn bCialencdeur cStocciaentyc,earns)esatriematnetdic3ip5,a6t6e0dnteowtianksetanpclaecseofinlivtehrecaUnnceitre(dincSltuadteins gdiunrtrinahgep20a1ti5c, baipleprdouxcimt caatenlcyertsh)reaer-equanartitceirpsaotefdwthoicthakaerepleaxcpeeicntetdhetoUbneitHedCSCt.atLeisvedrucrainngce2r0i1n5c,idaepnpcreoxriamteastealrye tahrroeuen-qdutahrrteerstiomf ewshhiicghhaerreinexapdeuclttemd atolebsethHaCnCin. Lwiovmerecna,nacnedr ihnacvideednocuebrlaetdesinareeacahrosuenxdovtheretehteimpaesst htwigohedreicnadadesul[t5m]. Lwiovmerecna,nacnedr ihnacvideednocuebrlaetdesinareeacahrosuenxdovtheretehteimpaesst htwigohedreicnadadesul[t5m]. aTlehse tmhaanjoirnitwy oomf eHnC, Cancdahseasveardeoautbtrleibduitnabelaechtoseuxndoverelryitnhge pinafsetcttwioonsdeccaaudseds [b5]y
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