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I Smith-Kielland

Publications and source records attributed to I Smith-Kielland.

13 recordsLinked to original sources
PubMed1996

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. Cytotoxicity evaluation was performed using Ehrlich ascites tumor cells. While cycloartenol induced no cytotoxic activity against Ehrlich ascites tumor cells, both isolated triterpenes exhibited cell inactivating effects. The IC50 is approximately 7.5 microM, while the IC90 is approximately 13.5 microM for 9,19-cycloart-25-ene-3 beta,24-diol. The 3 beta,25-diol compound is 50% less active.

Animals↗
PubMed1989

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. At higher sterol concentrations the 7 beta-hydroxy compound caused growth inhibition of the Ehrlich ascites cells, whereas the 7 alpha-hydroxylated sterol was ineffective. The rate of 7 alpha-dehydroxylation was, however, too low to be considered a likely pathway for detoxification. No other lipid-extractable products were detected, and no water-soluble products with influence on cell proliferation were present. Thus, the cytotoxicity is probably attributed to a property of the 7 beta-hydroxyl group of the (22R)-cholest-5-ene-3 beta,7 beta,22-triol.

Animals↗
PubMed1986

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. Tumor rates and tumor yields were calculated, and statistical assessment by accepted methods demonstrated a very significant inhibitory effect on tumor development in Groups A and B, as compared with Group C. The results indicate a growth-inhibitory effect during the induction period of carcinoma development. The influence on neoplastic growth of (22R)-cholest-5-ene-3 beta,7 alpha,22-triol, (22R)-cholest-5-ene-3 beta,7 beta,22-triol, and (22R)-cholest-5-ene-3 beta,22-diol-7-one was examined in suspension cultures of Ehrlich ascites tumor cells. The 7 alpha-hydroxy compound proved to be ineffective, whereas the latter two substances displayed a strong cytotoxic effect.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Inhibition of protein A24 lyase by nitrosoureas.

The protein A24 content of Ehrlich ascites tumor cells increased several-fold following treatment of cell cultures with nitrosoureas, but did not increase when other alkylating agents not containing carbamoyl moieties were tested. The same nitrosoureas and, in addition, 2-chloroethyl isocyanate inhibited an A24 lyase-containing cytoplasmic extract in cleaving protein A24 into histone H2A and ubiquitin. It appears that carbamoylation of A24 lyase by nitrosoureas inhibits the enzyme and is responsible for the measured increases in cellular protein A24 content due to reduced turnover of this protein.

Animals↗