White tea extract induces apoptosis in non-small cell lung cancer cells: the role of peroxisome proliferator-activated receptor-{gamma} and 15-lipoxygenases.
White tea extract induces apoptosis in non-small cell lung cancer cells: the role of peroxisome proliferator-activated receptor-{gamma} and 15-lipoxygenases.
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DOI：
10.1158/1940-6207.capr-09-0264
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Serio KJ
中科院分区：
文献类型：
--
作者：
Mao JT;Nie WX;Tsu IH;Jin YS;Rao JY;Lu QY;Zhang ZF;Go VL;Serio KJ
Emerging preclinical data suggests that tea possess anticarcinogenic and antimutagenic properties. We therefore hypothesize that white tea extract (WTE) is capable of favorably modulating apoptosis, a mechanism associated with lung tumorigenesis. We examined the effects of physiologically relevant doses of WTE on the induction of apoptosis in the nonsmall cell lung cancer (NSCLC) cell lines, A549 (adenocarcinoma) and H520 (squamous cell carcinoma) cells. We further characterized the molecular mechanisms responsible for the WTE-induced apoptosis, including the induction of PPAR-γ and the 15-lipoxygenase (15-LOX) signaling pathway. We found that WTE was effective in inducing apoptosis in both A549 and H520 cells, and inhibition of PPAR-γ with GW 9662 partially reversed the WTE-induced apoptosis. We further demonstrate that WTE increased PPAR-γ activation and mRNA expression, concomitantly increased 15-HETE release, and up-regulated 15-LOX-1 and 2 mRNA expression by A549 cells. Inhibition of 15-LOX with NGDA, as well as caffeic acid, abrogated the WTE-induced PPAR-γ activation and up-regulation of PPAR-γ mRNA expression in A549 cells. WTE also induced cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA expression and activated caspase 3. Inhibition of caspase 3 abrogated the WTE-induced apoptosis. Our findings indicate that WTE is capable of inducing apoptosis in NSCLC cell lines. The induction of apoptosis appears to be mediated, in part, through the up-regulation of the PPAR-γ and 15-LOX signaling pathways, with enhanced activation of caspase 3. Our findings support the future investigation of WTE as an antineoplastic and chemopreventive agent for lung cancer.
