Betuletol 3-methyl ether (BME) is a natural phenylbenzo-gamma-pyrone that inhibits cell proliferation in human tumor cell lines and induces apoptotic cell death in HL-60 cells. Here we show that BME displays strong cytotoxic properties in several human leukemia cell lines (U937, K-562, THP-1, Jurkat
5,7,3′-trihydroxy-3,4′-dimethoxyflavone-induced cell death in human Leukemia cells is dependent on caspases and activates the MAPK pathway
✍ Scribed by Fernando Torres; José Quintana; Francisco Estévez
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 400 KB
- Volume
- 49
- Category
- Article
- ISSN
- 0899-1987
- DOI
- 10.1002/mc.20619
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Flavonoids are polyphenolic compounds which display a vast array of biological activities and are promising anticancer agents. In this study we investigated the effect of 5,7,3′‐trihydroxy‐3,4′‐dimethoxyflavone (THDF) on viability of nine human tumor cell lines and found that it was highly cytotoxic against leukemia cells. THDF induced G~2~–M phase cell‐cycle arrest and apoptosis through a caspase‐dependent mechanism involving cytochrome c release, processing of multiple caspases (caspase‐3, ‐6, ‐7, and ‐9) and cleavage of poly(ADP‐ribose) polymerase. Overexpression of the protective mitochondrial proteins Bcl‐2 and Bcl‐x~L~ conferred partial resistance to THDF‐induced apoptosis. This flavonoid induced the phosphorylation of members of the mitogen‐activated protein kinases (MAPKs) family and cell death was attenuated by inhibition of c‐jun N‐terminal kinases/stress‐activated protein kinases (JNK/SAPK) and of extracellular signal‐regulated kinases (ERK) 1/2. In the present study we report that THDF‐induced cell death is mediated by an intrinsic dependent apoptotic event involving mitochondria and MAPKs, and through a mechanism independent of the generation of reactive oxygen species. The results suggest that THDF could be useful in the development of novel anticancer agents. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.
📜 SIMILAR VOLUMES
## Abstract Exogenous β~2~‐microglobulin (β~2~m) induces significant apoptosis in the CCRF‐HSB‐2 human lymphoblastic leukemia cell line as detected by DNA fragmentation, DAPI staining and annexin V binding assay. β~2~m treatment induced the release of cytochrome c and apoptosis‐inducing factor (AIF