Ho Hung-Yao, Cheng Mei-Ling, Chiu Hsin-Yu, Weng Shiue-Fen, Chiu Daniel Tsun-Yee
Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
Int J Oncol. 2008 Nov;33(5):969-77.
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.
已知脱氢表雄酮（DHEA）具有抗增殖作用。其机制尚未完全明确。我们研究了DHEA诱导肝癌细胞生长停滞的潜在机制。生长抑制与葡萄糖-6-磷酸脱氢酶（G6PD）活性增加相关，且对甲羟戊酸的逆转不敏感。因此，DHEA并非通过抑制G6PD和3-羟基-3-甲基戊二酰辅酶A还原酶（HMGR）发挥作用。相反，生长停滞伴随着细胞核编码的线粒体基因表达减少、线粒体形态和功能改变以及细胞内三磷酸腺苷（ATP）耗竭。相反，补充丙酮酸可减轻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。
