Quercetin exerts preferential cytotoxic effects on malignant mesothelioma cells by inducing p53 expression, caspase-3 activation, and apoptosis

Autor: Jun-Hwan Song, Kee-Min Woo, Yoon-Jin Lee, Sang-Han Lee, Ihl-Sung Park, Moon-Kyun Cho, Yong-Jin Lee, Myung-Ho Oh, Hae-Seon Nam
Rok vydání: 2015
Předmět:
Zdroj: Molecular & Cellular Toxicology. 11:295-305
ISSN: 2092-8467
1738-642X
DOI: 10.1007/s13273-015-0029-z
Popis: Quercetin, a naturally occurring flavonoid, has been heralded as a promising chemopreventive agent. This study was undertaken to probe the molecular mechanisms underlying the anti-cancer activity of quercetin in malignant mesothelioma (MM) cells. Quercetin at low doses elicited apoptotic cell death on MM MSTO-211H cells, as signified by pyknotic and fragmented nuclei, increased annexin V binding, and increased proportion of cells with hypodiploid DNA. Preceding these changes, quercetin induced up-regulation of p53 at both mRNA and protein levels without altering its ubiquitination, and increased caspase-3/7 activity with the resultant cleavages of procaspase-3 and PARP. Analyses of nuclear p53 level, p53 reporter gene, and RT-PCR toward p53-regulated genes demonstrated that induced p53 is transcriptionally active. The proportion of cells at sub-G0/G1 peak and G2/M phase increased in a quercetin concentration-dependent fashion, which were blocked by the pan-caspase inhibitor Z-VAD. Additionally, quercetin and gemcitabine produced a significant synergistic effect on inhibiting MS-TO-211H cell growth. Given that quercetin induced preferential p53-upregulating, growth-inhibiting, and apoptosis-activating effects on MM cells, the use of quercetin may be a potential therapeutic strategy for enhancing anti-cancer efficacy of existing chemotherapy in MM.
Databáze: OpenAIRE
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