title: Actein inhibits the Na+-K+-ATPase and enhances the growth inhibitory effect of digitoxin on human breast cancer cells.
abstract: The Na+K+-ATPase is a known target of cardiac glycosides such as digitoxin and ouabain. We determined that the enzyme also is a target of the structurally-related triterpene glycoside actein, present in the herb black cohosh. Actein's inhibition of Na+-K+-ATPase activity was less potent than that of digitoxin, but actein potentiated digitoxin's inhibitory effect on Na+-K+-ATPase activity and MDA-MB-453 breast cancer cell growth. We observed different degrees of signal amplification for the two compounds. Actein's inhibitory effect on ATPase activity was amplified 2-fold for cell growth inhibition, whereas digitoxin's signal was amplified 20-fold. Actein induced a biphasic response in proteins downstream of ATPase: low dose and short duration of treatment upregulated NF-kappaB promoter activity, p-ERK, p-Akt and cyclin D1 protein levels, whereas higher doses and longer exposure inhibited these activities. Actein and digitoxin may be a useful synergistic combination for cancer chemoprevention and/or therapy.
authors.affiliation: Department of Rehabilitation Medicine, College of Physicians and Surgeons, Columbia University, HHSC-1508, 701 W. 168th Street, New York, NY 10032, USA. le2012@columbia.edu
authors.forename: Linda Saxe
authors.initials: LS
authors.lastname: Einbond
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.forename: Hangbao
authors.initials: H
authors.lastname: Ma
authors.forename: Hsan-Au
authors.initials: HA
authors.lastname: Wu
authors.forename: Sarah
authors.initials: S
authors.lastname: Goldsberry
authors.forename: Serge
authors.initials: S
authors.lastname: Sicular
authors.forename: Maya
authors.initials: M
authors.lastname: Panjikaran
authors.forename: Giannicola
authors.initials: G
authors.lastname: Genovese
authors.forename: Erica
authors.initials: E
authors.lastname: Cruz