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-κB 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.
Original language | English |
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Pages (from-to) | 608-613 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 375 |
Issue number | 4 |
DOIs | |
State | Published - 31 Oct 2008 |
Externally published | Yes |
Keywords
- Cardiac glycoside
- Synergy
- Triterpene glycoside