Quercetin exerts preferential cytotoxic effects on malignant mesothelioma cells by inducing p53 expression, caspase-3 activation, and apoptosis
- Abstract
- 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-G(0)/G(1) peak and G(2)/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.
- All Author(s)
- Y. J. Lee
; I. S. Park
; J. H. Song
; M. H. Oh
; H. S. Nam
; M. K. Cho
; K. M. Woo
; S. H. Lee
- Issued Date
- 2015
- Type
- Article
- Keyword
- p53; Malignant mesothelioma; Apoptosis; Caspase-3; Synergistic cytotoxicity
- Publisher
- 대한독성유전단백체학회
The Korean Society of Toxicogenomics and Toxicoproteomics
- ISSN
- 1738-642X
; 2092-8467
- Citation Title
- Molecular & cellular toxicology
- Citation Volume
- 11
- Citation Number
- 3
- Citation Start Page
- 295
- Citation End Page
- 305
- Language(ISO)
- eng
- DOI
- 10.1007/s13273-015-0029-z
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/2471
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