Cytotoxic triterpenoids from the leaves of Euphorbia pulcherrima.

Two cytotoxic triterpenes have been isolated from Euphorbia pulcherrima. Their structures and stereochemistry have been established from NMR, IR, and EI-mass spectroscopy. The compounds were identified as 9,19-cycloart-23-ene-3 beta,25-diol and, 9,19-cycloart-25-ene-3 beta,24-diol.

Difference in cytotoxicity of (22R)-cholest-5-ene-3 beta,7 alpha,22-triol and (22R)-cholest-5-ene-3 beta,7 beta,22-triol is not explained by different patterns of metabolites.

Ehrlich ascites tumor cells in suspension culture were incubated with the plant-derived sterol isomers (22R)-cholest-5-ene-3 beta,7 alpha,22-triol and (22R)-cholest-5-ene-3 beta,7 beta,22-triol. Both sterols were 7-dehydroxylated by the neoplastic cells, and the product was identified as (22R)-22-hydroxycholesta-4,6-dien-3-one. At sub-toxic sterol concentrations the conversion of the 7 alpha-hydroxy compound was about 5 times higher than that of the 7 beta-isomer.

Inhibitory effect of an oxygenated cholesterol on the induction and progression of DMBA-induced mammary carcinomas in the rat.

In vivo studies on the effect of two stereoisomeric 7,22-dihydroxycholesterols on tumor development were conducted in the Charles Huggins animal cancer model (DMBA-induced mammary cancer in the Sprague-Dawley female rat). Three groups of DMBA-treated animals were fed a 9:1 mixture of (22R)-cholest-5-ene-3 beta,7 beta,22-triol and (22R)-cholest-5-ene-3 beta,7 alpha,22-triol in the drinking water in a calculated dose of 250 micrograms per animal per day. One group (A) received the sterols throughout the experimental period of 35 weeks, another group (B) during the first 12 weeks only, and a third group (C) only during weeks 13 through 35 after DMBA injection.