Cardenolides and cancer

Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization

“…The growing body of epidemiological (19,20), in vitro (18), and in vivo (31) evidence supporting the anticancer benefits of cardenolides has prompted the search for noncardioactive analogs that retain anticancer activity. The specific mechanism of cardenolide-induced cytotoxicity remains controversial.…”

“…In addition to its well known cardiac activity, which is mediated by inhibition of the plasma membrane Na ϩ ͞K ϩ -ATPase (17), digitoxin has demonstrated in vitro anticancer properties (18), and patient profiling suggests the survival rate of cancer patients taking digitoxin is statistically enhanced (19,20). Cardiac glycosides were also recently noted to inhibit the expression of four genes that are overexpressed in prostate cancer cells, including transcription factors and the apoptosis inhibitor survivin (21), and to provide protective effects against polyglutamine-based diseases (22).…”

High-Throughput Screening Identifies Cardiac Glycosides as Potent Inhibitors of Human Tissue Kallikrein Expression: Implications for Cancer Therapies

“…Strong evidence now supports the anticancer properties of these drugs. Early epidemiologic studies by Stenkvist et al reported significantly lower mortality rates of cancer patients under cardiac glycoside treatment (25,26). Because then, numerous in vitro studies have reported potent antiproliferative effects of these compounds in a panel of cancer cell lines, including breast (27), prostate (28), melanoma (29), pancreatic (30), lung (31), leukemia (32), neuroblastoma (33), and renal adenocarcinoma (ref.…”

Identification of cardiac glycosides in fractions from Periploca forrestii by high-performance liquid chromatography/diode-array detection/electrospray ionization multi-stage tandem mass spectrometry and liquid chromatography/nuclear magnetic resonance

“…Cardiac glycosides are a class of natural products that are used clinically to increase cardiac contractile force in patients with congestive heart failure and cardiac arrhythmias. Recently, epidemiological data [4][5] along with reports based on both the in vitro [6][7][8] and in vivo [9][10] demonstration of cardiac glycosides-mediated anti-cancer activity further emphasize the possibility of developing this class of compounds as antitumor agents. Therefore, the development of a reliable analytical method for cardiac glycosides can benefit the rapid identification and targeted isolation of new cardiac glycosides in plant extracts.…”

“…As a result, a total of nine trace cardiac glycosides (peaks 1-9) were tentatively determined. Of these, eight (2)(3)(4)(5)(6)(7)(8)(9) are new compounds and one (1) is reported from P. forrestii for the first time.…”