Quercetin exerts preferential cytotoxic effects on malignant mesothelioma cells by inducing p53 expression, caspase-3 activation, and apoptosis
- Authors
- Lee, Yoon-Jin; Lee, Yong-Jin; Park, Ihl-Sung; Song, Jun-Hwan; Oh, Myung-Ho; Nam, Hae-Seon; Cho, Moon-Kyun; Woo, Kee-Min; Lee, Sang-Han
- Issue Date
- Sep-2015
- Publisher
- 대한독성 유전단백체 학회
- Keywords
- p53; Malignant mesothelioma; Apoptosis; Caspase-3; Synergistic cytotoxicity
- Citation
- Molecular & Cellular Toxicology, v.11, no.3, pp 295 - 305
- Pages
- 11
- Journal Title
- Molecular & Cellular Toxicology
- Volume
- 11
- Number
- 3
- Start Page
- 295
- End Page
- 305
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/10322
- DOI
- 10.1007/s13273-015-0029-z
- ISSN
- 1738-642X
2092-8467
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Dermatology > 1. Journal Articles
- College of Medicine > Department of Clinical Parasitology > 1. Journal Articles
- College of Medicine > Department of Pediatrics > 1. Journal Articles
- College of Medicine > Department of Occupational Medicine > 1. Journal Articles
- College of Medicine > Department of Biochemistry > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.