Actein inhibits the Na+-K+-ATPase and enhances the growth inhibitory effect of digitoxin on human breast cancer cells

作者：Einbond Linda Saxe^*; Shimizu Masahito; Ma Hangbao; Wu Hsan au; Gold**erry Sarah; Sicular Serge; Panjikaran Maya; Genovese Giannicola; Cruz Erica

来源：Biochemical and Biophysical Research Communications, 2008, 375(4): 608-613.

DOI：10.1016/j.bbrc.2008.08.054

• Triterpene glycoside
• Cardiac glycoside
• Synergy

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-kappa B 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.

• 出版日期2008-10-31