White tea extract induces apoptosis in non-small cell lung cancer cells: the role of peroxisome proliferator-activated receptor-{gamma} and 15-lipoxygenases.

Abstract

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 non-small cell lung cancer cell lines A549 (adenocarcinoma) and H520 (squamous cell carcinoma) cells. We further characterized the molecular mechanisms responsible for WTE-induced apoptosis, including the induction of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and the 15-lipoxygenase (15-LOX) signaling pathways. We found that WTE was effective in inducing apoptosis in both A549 and H520 cells, and inhibition of PPAR-gamma with GW9662 partially reversed WTE-induced apoptosis. We further show that WTE increased PPAR-gamma activation and mRNA expression, concomitantly increased 15(S)-hydroxy-eicosatetraenoic acid release, and upregulated 15-LOX-1 and 15-LOX-2 mRNA expression by A549 cells. Inhibition of 15-LOX with nordihydroguaiaretic acid (NGDA), as well as caffeic acid, abrogated WTE-induced PPAR-gamma activation and upregulation of PPAR-gamma mRNA expression in A549 cells. WTE also induced cyclin-dependent kinase inhibitor 1A mRNA expression and activated caspase-3. Inhibition of caspase-3 abrogated WTE-induced apoptosis. Our findings indicate that WTE is capable of inducing apoptosis in non-small cell lung cancer cell lines. The induction of apoptosis seems to be mediated, in part, through the upregulation of the PPAR-gamma 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.

• Authors: Jenny T Mao, Wen-Xian Nie, I-Hsien Tsu, Yu-Sheng Jin, Jian Yu Rao, Qing-Yi Lu, Zuo-Feng Zhang, Vay Liang W Go, Kenneth J Serio
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 3 Issue 9 Pg. 1132-40 (Sep 2010) ISSN: 1940-6215 [Electronic] United States
• PMID: 20668019 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 2-chloro-5-nitrobenzanilide
• Anilides
• Hormone Antagonists
• Hydroxyeicosatetraenoic Acids
• PPAR gamma
• Plant Extracts
• Tea
• 15-hydroxy-5,8,11,13-eicosatetraenoic acid
• Catechin
• epigallocatechin gallate
• Arachidonate 15-Lipoxygenase

Topics

• Anilides (pharmacology)
• Apoptosis (drug effects)
• Arachidonate 15-Lipoxygenase (genetics, metabolism, physiology)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology, prevention & control)
• Catechin (analogs & derivatives, pharmacology, therapeutic use)
• Drug Evaluation, Preclinical
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Hormone Antagonists (pharmacology)
• Humans
• Hydroxyeicosatetraenoic Acids (pharmacology)
• Lung Neoplasms (genetics, metabolism, pathology, prevention & control)
• PPAR gamma (antagonists & inhibitors, genetics, metabolism, physiology)
• Plant Extracts (pharmacology, therapeutic use)
• Tea (chemistry)
• Tumor Cells, Cultured