Antiproliferative cardenolides from Periploca graeca.
Nine cardiotonic steroids, six 17beta-cardenolides (2, 4, 6-9) and three 17alpha-cardenolides (1, 3, 5) have been identified from the chloroform and chloroform-methanol extracts of Periploca graeca L. (Asclepiadaceae) stems. Among these, compound 5, the 17alpha-isomer of periplocin 6, was identified as a new compound. The antiproliferative effects of these compounds were tested in vitro in the hormone-independent prostate cancer cell line PC-3. Five of these compounds, all 17beta-isomers with a 14beta-OH group and at least one sugar molecule (4, 6-9), showed a very strong antiproliferative effect, with IC50 values between 18 and 50 nM. Compound 2, the only 17beta-cardenolide aglycone, had an IC50 value of 0.6 microM, which is 13 to 16 times higher than the values found for the corresponding cardenolides with one or two sugars. The IC50 values found for the three 17alpha-isomers were significantly higher (5.4 and 7.3 microM), with IC50 ratios (17alpha-cardenolide/17beta-cardenolide) of up to 192. In the 17alpha-cardenolide series, the presence of a sugar unit does not seem to have a significant effect on the IC50 values. This is the first report showing a markedly different cytotoxicities between the 17alpha- and 17beta-isomers in the cardenolide series.
Spera
Daniela
D
Dipartimento di Chimica Bioorganica e Biofarmacia, Università di Pisa, Pisa, Italy.
Siciliano
Tiziana
T
De Tommasi
Nunziatina
N
Braca
Alessandra
A
Vessières
Anne
A
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002298:Cardenolides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology; D031109:Periploca; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D002298:Cardenolides; D010936:Plant Extracts