Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

Table 1

The antitumor activity of cardiac glycosides in mice xenografted with human cancer cells is probably caused by their ability to selectively kill human cells versus rodent cells rather than by their ability to selectively kill human cancer cells versus human nonmalignant cells.

Cardiac glycoside	Antitumor activity in mice xenografted with human cancer cells	Selective cytotoxicity against human cells versus rodent cells	Selective cytotoxicity against human cancer cells versus human nonmalignant cells
Arenobufagin	Liver HepG2/ADM [28]	N.D.	N.D.
Bufalin	Breast MDA-MB-231 [19], osteosarcoma U2OS/MTX300 [50], and pancreatic Mia Paca-2 [49]	>1000-fold [29]	NO: breast cancer versus breast nonmalignant [23]; 10-fold: ovarian cancer versus endometrial nonmalignant [53]
Bufotalin	Liver R-HepG2 [51]	>100-fold [54]	N.D.
Digitoxin	N.D.	>1000-fold [29]; >700-fold [24]	10-fold: lung cancer versus lung nonmalignant [24]; 3-fold: lung cancer versus lung nonmalignant [55]; 7-fold: ALL versus PBMCs nonmalignant [15]; 4-fold: AML versus PBMCs nonmalignant [15]; 2-fold: CLL versus PBMCs nonmalignant [15]; 2-fold: breast cancer versus breast nonmalignant [24]; NO: breast cancer versus breast nonmalignant [23]; NO: skin cancer versus skin nonmalignant [24]
Digoxin	Brain SH-SY5Y [33], brain SK-N-AS [33], breast MDA-MB-231 [36, 37], breast MDA-MB-435 [35], liver Hep3B [17], prostate PC3 [17], prostate PPC-1 [34], and transformed human B-lymphocytes P493-Myc [17]	>1000-fold [24, 29]	NO: breast cancer versus breast nonmalignant [24]; 8- fold: lung cancer versus lung nonmalignant [24]; NO: skin cancer versus skin nonmalignant [24]; 8-fold: brain cancer versus umbilical vein endothelial nonmalignant [33]; NO: breast cancer versus umbilical vein endothelial nonmalignant [33]; NO: colorectal cancer versus umbilical vein endothelial nonmalignant [33]
Lanatoside C	Brain U87 [48]	>100-fold [29]	N.D.
Ouabain	Brain SH-SY5Y [27], ocular Y79LUC [39], pancreatic BON1 [40], promyelocytic leukemia HL-60 [18], and prostate PPC-1 [40]	>1000-fold [24, 29, 44]	NO: breast cancer versus breast nonmalignant [23, 24]; 5- fold: lung cancer versus lung nonmalignant [24]; NO: skin cancer versus skin nonmalignant [24]; 2-fold: ALL versus PBMCs nonmalignant [15]; 2-fold: AML versus PBMCs nonmalignant [15]; NO: CLL versus PBMCs nonmalignant [15]
Periplocin	Liver Huh-7 [47] and lung A549 [46]	>1000-fold [47]*; NO: [46]	>1000-fold: liver cancer versus PBMCs nonmalignant [47]*
UNBS1450	Brain U373-MG [44], lung A549 [41, 42], lung NCI-H727 [41, 42], prostate PC-3 [43], and skin VM-48 [45]	>100-fold [44]	10-fold: brain cancer versus lung and skin nonmalignant [44]; 100-fold: prostate cancer versus lung and skin nonmalignant [43]

N.D.: not determined; NO: no selective cytotoxicity; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; CLL: chronic lymphocytic leukemia; PBMCs: peripheral blood mononuclear cells; *not specified if the PBMCs were human cells or rodent cells (we contacted the authors without success).