This article was published online on 15 Nov 2011 and an error was subsequently identified with an author's name. Nicola Normanno was wrongly spelled as Nicola Normano. This has now been corrected on 6 March 2012.
Quercetin-3-methyl ether inhibits lapatinib-sensitive and -resistant breast cancer cell growth by inducing G2/M arrest and apoptosis†
Article first published online: 15 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 52, Issue 2, pages 134–143, February 2013
How to Cite
Li, J., Zhu, F., Lubet, R. A., De Luca, A., Grubbs, C., Ericson, M. E., D'Alessio, A., Normanno, N., Dong, Z. and Bode, A. M. (2013), Quercetin-3-methyl ether inhibits lapatinib-sensitive and -resistant breast cancer cell growth by inducing G2/M arrest and apoptosis. Mol. Carcinog., 52: 134–143. doi: 10.1002/mc.21839
- Issue published online: 17 JAN 2013
- Article first published online: 15 NOV 2011
- Manuscript Accepted: 19 OCT 2011
- Manuscript Revised: 14 OCT 2011
- Manuscript Received: 28 JUL 2011
- breast cancer;
- natural product;
- quercetin-3-methyl ether;
Lapatinib, an oral, small-molecule, reversible inhibitor of both EGFR and HER2, is highly active in HER2 positive breast cancer as a single agent and in combination with other therapeutics. However, resistance against lapatinib is an unresolved problem in clinical oncology. Recently, interest in the use of natural compounds to prevent or treat cancers has gained increasing interest because of presumed low toxicity. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity. Here, we found that quercetin-3-methyl ether caused a significant growth inhibition of lapatinib-sensitive and -resistant breast cancer cells. Western blot data showed that quercetin-3-methyl ether had no effect on Akt or ERKs signaling in resistant cells. However, quercetin-3-methyl ether caused a pronounced G2/M block mainly through the Chk1-Cdc25c-cyclin B1/Cdk1 pathway in lapatinib-sensitive and -resistant cells. In contrast, lapatinib produced an accumulation of cells in the G1 phase mediated through cyclin D1, but only in lapatinib-sensitive cells. Moreover, quercetin-3-methyl ether induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7, and poly(ADP-ribose) polymerase (PARP) in both cell lines. Overall, these results suggested that quercetin-3-methyl ether might be a novel and promising therapeutic agent in lapatinib-sensitive or -resistant breast cancer patients. © 2011 Wiley Periodicals, Inc.