Apoptosis in human hepatoma cell line induced by 4,5-didehydro geranylgeranoic acid (acyclic retinoid) via down-regulation of transforming growth factor-alpha
Apoptosis in human hepatoma cell line induced by 4,5-didehydro geranylgeranoic acid (acyclic retinoid) via down-regulation of transforming growth factor-alpha
复制标题
DOI：
10.1006/bbrc.1996.0188
复制
发表时间：
1996-02-06
影响因子：
3.1
通讯作者：
Muto, Y
中科院分区：
文献类型：
--
作者：
Nakamura, N;Shidoji, Y;Muto, Y
合成的4，5-二羟GGA（香叶基香叶酸）是细胞视黄酸结合蛋白和核视黄酸受体的有效配体，其在人肝癌衍生细胞系HuH-7中诱导凋亡，但在原代肝细胞中不诱导凋亡，尽管全反式或9-顺式视黄酸不诱导任何生长抑制。外源性转化生长因子-α（TGF-α）或表皮生长因子（EGF）在4，5-二氨基葡萄糖酸存在下阻止细胞凋亡，但肝细胞生长因子、胰岛素样生长因子-II、胰岛素或三碘甲状腺原氨酸基本上无活性。4，5-二硫代GGA处理后30 min显著下调TGF α mRNA水平。抗TGF α或抗EGF受体单克隆抗体在不使用酸的情况下诱导HuH-7细胞凋亡。综上所述，本研究强烈表明，4，5-二氨基GGA通过由于下调TGF α基因表达而破坏由TGF α和EGF受体组成的自分泌环来诱导HuH-7细胞的凋亡。(C)出版社：Academic Press，Inc.
Synthetic 4, 5-didehydro GGA (geranylgeranoic acid), a potent ligand both for cellular retinoic acid-binding protein and for nuclear retinoid receptors, induced apoptosis in human hepatoma-derived cell line HuH-7 but not in primary hepatocytes, although all-trans or 9-cis retinoic acid did not induce any growth inhibition. Either exogenous transforming growth factor-alpha (TGF alpha) or epidermal growth factor (EGF) prevented the cells from apoptosis in the presence of 4, 5-didehydro GGA, but hepatocyte growth factor, insulin-like growth factor-II, insulin or triiodothyronine was essentially inactive. 4,5-Didehydro GGA down-regulated the cellular levels of TGF alpha mRNA as rally as 30 min after the treatment. Either anti-TGF alpha or anti-EGF receptor monoclonal antibody induced apoptosis in HuH-7 cells without using the acid. Taken together, the present study strongly suggests that 4,5-didehydro GGA induced apoptosis in HuH-7 cells through the destruction of autocrine loop consisting of TGF alpha and EGF receptor due to the down-regulation of TGF alpha gene expression. (C) 1996 Academic Press, Inc.