Identification and biological activities of new taccalonolide microtubule stabilizers.

The taccalonolides are a unique class of microtubule stabilizers that do not bind directly to tubulin. Three new taccalonolides, Z, AA, and AB, along with two known compounds, taccalonolides R and T, were isolated from Tacca chantrieri and Tacca integrifolia. Taccalonolide structures were determined by 1D and 2D NMR methods.

Evelynin, a cytotoxic benzoquinone-type Retro-dihydrochalcone from Tacca chantrieri.

A new benzoquinone-type retro-dihydrochalcone, named evelynin, was isolated from the roots and rhizomes of Tacca chantrieri. The structure was elucidated on the basis of the analysis of spectroscopic data and confirmed by a simple one-step total synthesis. Evelynin exhibited cytotoxicity against four human cancer cell lines, MDA-MB-435 melanoma, MDA-MB-231 breast, PC-3 prostate, and HeLa cervical carcinoma cells, with IC(50) values of 4.

The taccalonolides: microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms.

The taccalonolides are a class of structurally and mechanistically distinct microtubule-stabilizing agents isolated from Tacca chantrieri. A crucial feature of the taxane family of microtubule stabilizers is their susceptibility to cellular resistance mechanisms including overexpression of P-glycoprotein (Pgp), multidrug resistance protein 7 (MRP7), and the betaIII isotype of tubulin. The ability of four taccalonolides, A, E, B, and N, to circumvent these multidrug resistance mechanisms was studied.

Programming of initial steps in bile acid synthesis by breast-feeding vs. formula-feeding in the baboon.

We tested the hypothesis that breast- vs. formula-feeding differentially affects the enzymatic activity of three sterol hydroxylases critical in the initial steps of bile acid formation. Thirty baboons were either breast-fed or formula-fed for the first 14 wk of life before weaning to baboon chow.

Taccalonolides E and A: Plant-derived steroids with microtubule-stabilizing activity.

During the course of a mechanism-based screening program designed to identify new microtubule-disrupting agents from natural products, we identified a crude extract from Tacca chantrieri that initiated Taxol-like microtubule bundling. Bioassay-directed purification of the extract yielded the highly oxygenated steroids taccalonolides E and A. The taccalonolides caused an increased density of cellular microtubules in interphase cells and the formation of thick bundles of microtubules similar to the effects of Taxol.

High and low responding strains of laboratory opossums differ in sterol 27-hydroxylase and acyl-coenzyme A:cholesterol acyltransferase activities on a high cholesterol diet.

Two partially inbred strains of laboratory opossums exhibit extremely high or low levels of VLDL+LDL cholesterol concentrations, respectively, when challenged with a high cholesterol and high fat diet. The present studies were conducted to determine whether the high and low responding strains differ in activities of important enzymes that have been shown to affect lipemic responsiveness to diet. We measured plasma 27-hydroxycholesterol and hepatic activities of 27-hydroxylase and 7alpha-hydroxylase in high and low responding opossums while consuming the basal diet and cholesterol-enriched diets.