Abstract
Adiponectin exhibits potent antitumor activities. Herein, we examined the molecular mechanisms underlying suppression of tumor growth by globular adiponectin (gAcrp). We demonstrated that gAcrp suppressed B‐cell lymphoma 2 (Bcl‐2) expression, an anti‐apoptotic gene, by inducing its mRNA destabilization, which was accompanied with a decrease in cell viability and increased caspase‐3 activity in hepatic cancer cells. In addition, gAcrp increased expression of tristetraprolin (TTP) and AU‐rich element RNA‐binding protein 1 (AUF1), which are mRNA stability regulatory proteins. Moreover, gAcrp‐induced suppression of Bcl‐2 expression was abrogated by knockdown of TTP or AUF1. These data indicate that gAcrp induces apoptosis of hepatic cancer cells by TTP‐ and AUF1‐mediated Bcl‐2 mRNA destabilization, and further suggest that TTP and AUF1 are novel targets mediating the antitumor activity of adiponectin.
Highlights
Recent studies have revealed that adiponectin decreases Bcl-2 expression [4]; the molecular mechanism by Abbreviations 30-UTR, 30-untranslated region; adipoR1, adiponectin receptor type 1; adipoR2, adiponectin receptor type 2; AMPK, adenosine monophosphate-activated protein kinase; ARE, A +U-rich elements; AUF1, AU-rich element RNA-binding protein 1; Bcl-2, B-cell lymphoma 2; DMEM, Dulbecco’s modified eagle medium; FBS, fetal bovine serum; gAcrp, globular adiponectin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HepG2, human hepatoma cancer cells; HRP, horseradish peroxidase; IL-3, interleukin-3; MCF-7, human breast cancer cells; MTS, 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; PBS, phosphate buffer saline; PPAR-a, peroxisome proliferator-activated receptor alpha; PVDF, polyvinylidene difluoride; quantitative realtime polymerase chain reaction (qRT-PCR), quantitative real-time polymerase chain reaction; TTP, tristetraprolin
We have demonstrated for the first time that gAcrp induces Bcl2 mRNA destabilization in hepatic cancer cells
TTP induction and AUF1 induction play a crucial role in Bcl-2 mRNA destabilization and suppression of hepatic cancer cell growth by gAcrp
Summary
GAcrp-induced suppression of Bcl-2 expression was abrogated by knockdown of TTP or AUF1 These data indicate that gAcrp induces apoptosis of hepatic cancer cells by TTP- and AUF1-mediated Bcl-2 mRNA destabilization, and further suggest that TTP and AUF1 are novel targets mediating the antitumor activity of adiponectin. Recent studies have revealed that adiponectin decreases Bcl-2 expression [4]; the molecular mechanism by Abbreviations 30-UTR, 30-untranslated region; adipoR1, adiponectin receptor type 1; adipoR2, adiponectin receptor type 2; AMPK, adenosine monophosphate-activated protein kinase; ARE, A (adenylate) +U (uridylate)-rich elements; AUF1, AU-rich element RNA-binding protein 1; Bcl-2, B-cell lymphoma 2; DMEM, Dulbecco’s modified eagle medium; FBS, fetal bovine serum; gAcrp, globular adiponectin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HepG2, human hepatoma cancer cells; HRP, horseradish peroxidase; IL-3, interleukin-3; MCF-7, human breast cancer cells; MTS, 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; PBS, phosphate buffer saline; PPAR-a, peroxisome proliferator-activated receptor alpha; PVDF, polyvinylidene difluoride; qRT-PCR, quantitative real-time polymerase chain reaction; TTP, tristetraprolin. Adiponectin inhibits tumor growth by TTP and AUF1 which adiponectin suppresses Bcl-2 expression in cancer cells is not well defined
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