Leptin counteracts sodium butyrate-induced apoptosis in human colon cancer HT-29 cells via NF-κB signaling

被引:120
作者
Rouet-Benzineb, R
Aparicio, T
Guilmeau, S
Pouzet, C
Descatoire, V
Buyse, M
Bado, A
机构
[1] Univ Paris 07, Lab Neuroendocrinol & Biol Cellulaire Digest, INSERM, U410, F-75860 Paris 18, France
[2] IFR 02, Serv Confocale, F-75860 Paris 18, France
[3] IFR 02, Serv Cytometrie Flux Digest, F-75860 Paris 18, France
关键词
D O I
10.1074/jbc.M312999200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study shows that leptin induced a rapid phosphorylation of p42/44 mitogen-activated protein kinase, an enhancement of both NF-kappaB DNA binding and transcriptional activities, and a concentration-dependent increase of HT-29 cell proliferation. These effects are consistent with the presence of leptin receptors on cell membranes. The leptin induction of cell growth was associated with an increase of cell population in S and G(2)/M phase compared with control cells found in G(0)/G(1) phase of the cell cycle. Moreover, cyclin D1 immunoreactivity was enhanced in leptin-treated HT-29 cells and this increase was essentially associated with cell population in G(0)/G(1) phase. On the other hand, we observed that sodium butyrate inhibited cell proliferation by blocking HT-29 cells in G(0)/G(1) phase of the cell cycle. Interestingly, at physiological concentration, leptin prevented sodium butyrate-induced morphological nucleus changes, DNA laddering and suppressed butyrate-induced cell cycle arrest. This anti-apoptotic effect of leptin was associated with HT-29 cell proliferation and activation NF-kappaB pathways. However, the phosphorylation of p42/44 MAP kinase in response to leptin was reduced in butyrate-treated cells. These data demonstrated that leptin is a potent mitogenic factor for intestinal epithelial cells through the MAP kinase and NF-kappaB pathways. They also showed, for the first time, that leptin promotes colon cancer HT-29 cell survival upon butyrate challenge by counteracting the apoptotic programs initiated by this short chain fatty acid probably through the NF-kappaB pathways. Although further studies are required to unravel the precise mechanism, these data may have significance in the pathogenesis of colorectal cancer and ulcerative colitis diseases.
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页码:16495 / 16502
页数:8
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