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

被引：34

作者：

Einbond, Linda Saxe ^{[1
]}

Shimizu, Masahito ^{[2
]}

Ma, Hangbao ^{[1
]}

Wu, Hsan-au ^{[1
]}

Goldsberry, Sarah ^{[1
]}

Sicular, Serge ^{[1
]}

Panjikaran, Maya ^{[1
]}

Genovese, Giannicola ^{[2
]}

Cruz, Erica ^{[1
]}

机构：

[1] Columbia Univ, Dept Rehabil Med, Coll Phys & Surg, New York, NY 10032 USA

[2] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Coll Phys & Surg, New York, NY 10032 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 375卷 / 04期

关键词：

Triterpene glycoside; Cardiac glycoside; Synergy;

D O I：

10.1016/j.bbrc.2008.08.054

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：608 / 613

页数：6

共 21 条

[1] Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels [J].

Arispe, Nelson ;

Diaz, Juan Carlos ;

Simakova, Olga ;

Pollard, Harvey B. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (07) :2610-2615

[2]

Einbond L. S., 2007, PHYTOMEDICINE

[3] The growth inhibitory effect of actein on human breast cancer cells is associated with activation of stress response pathways [J].

Einbond, Linda Saxe ;

Sue, Tao ;

Wu, Hsan-au ;

Friedman, Richard ;

Wang, Xiaomei ;

Ramirez, Alejandro ;

Kronenberg, Fredi ;

Weinstein, I. Bernard .

INTERNATIONAL JOURNAL OF CANCER, 2007, 121 (09) :2073-2083

[4]

Einbond LS, 2007, ANTICANCER RES, V27, P697

[5] Actein and a fraction of black cohosh potentiate antiproliferative effects of chemotherapy agents on human breast cancer cells [J].

Einbond, Linda Saxe ;

Shimizu, Masahito ;

Nuntanakorn, Paiboon ;

Seter, Colette ;

Cheng, Rong ;

Jiang, Bei ;

Kronenberg, Fredi ;

Kennelly, Edward J. ;

Weinstein, I. Bernard .

PLANTA MEDICA, 2006, 72 (13) :1200-1206

[6] Growth inhibitory activity of extracts and purified components of black cohosh on human breast cancer cells [J].

Einbond, LS ;

Shimizu, M ;

Xiao, DH ;

Nuntanakorn, P ;

Lim, JTE ;

Suzui, M ;

Seter, C ;

Pertel, T ;

Kennelly, EJ ;

Kronenberg, F ;

Weinstein, IB .

BREAST CANCER RESEARCH AND TREATMENT, 2004, 83 (03) :221-231

[7]

Foster S., 1999, HerbalGram, P35

[8] INHIBITION OF RAT-BRAIN NA+-K+-ATPASE BY TRITERPENE GLYCOSIDES FROM HOLOTHURIANS [J].

GORSHKOVA, IA ;

GORSHKOV, BA ;

STONIK, VA .

TOXICON, 1989, 27 (08) :927-936

[9] Two different modes of inhibition of the rat brain Na+,K+ -ATPase by triterpene glycosides, psolusosides A and B from the holothurian Psolus fabricii [J].

Gorshkova, IA ;

Kalinin, VI ;

Gorshkov, BA ;

Stonik, VA .

COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY, 1999, 122 (01) :101-108

[10]

Haas M, 2000, J BIOL CHEM, V275, P27832

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