Dehydroepiandrosterone induces growth arrest of hepatoma cells via alteration of mitochondrial gene expression and function
Dehydroepiandrosterone induces growth arrest of hepatoma cells via alteration of mitochondrial gene expression and function
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DOI：
10.3892/ijo_00000084
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发表时间：
2008-11-01
影响因子：
5.2
通讯作者：
Chiu, Daniel Tsun-Yee
中科院分区：
文献类型：
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作者：
Ho, Hung-Yao;Cheng, Mei-Ling;Chiu, Daniel Tsun-Yee
已知DHEA具有抗增殖作用。其机制尚未完全了解。我们研究了DHEA诱导肝癌细胞生长停滞的机制。生长抑制与G6 PD活性增加有关，对甲羟戊酸逆转不敏感。因此，DHEA不通过抑制G6 PD和HMGR起作用。相反，生长停滞伴随着细胞核编码的线粒体基因的表达减少;线粒体的形态和功能改变;以及细胞内ATP的耗尽。相反，丙酮酸补充减轻了DHEA诱导的生长抑制。DHEA可能通过改变线粒体基因表达、形态和功能来抑制细胞生长。
DHEA is known to have anti-proliferative effect. The mechanism is not completely understood. We investigated the mechanism underlying DHEA-induced growth arrest of hepatoma cells. Growth inhibition was associated with increased G6PD activity, and insensitive to reversal by mevalonate. Thus, DHEA does not act via inhibition of G6PD and HMGR. Instead, growth stagnation was accompanied by reduced expression of nucleus-encoded mitochondrial genes; morphological and functional alterations of mitochondria; and depletion of intracellular ATP. Conversely, pyruvate supplementation alleviated DHEA-induced growth inhibition. It is likely that DHEA suppresses cell growth by altering mitochondrial gene expression, morphology and functions.