Taxol-resistant colon cell

In MDR cells, a significant fraction of P-gp is found associated with caveolin-rich membranes, and there is a substantial increase in the number of caveolae and caveolin-1 protein level. For example, both multidrug resistant human colon adenocarcinoma HT-29 cells and adriamycin-resistant breast adenocarcinoma MCF-7 cells display about a 12-fold increase in caveolin expression, which correlates with an approximate fivefold increase in morphologically identifiable caveolae [55], In addition, these cells exhibit increased amounts of phospholipase D and lipids such as cholesterol, glucosylceramide, and sphingomyelin [56, 57], Similarly, taxol-resistant A549 cells display both increased caveolin expression and caveolae numbers [58], While these correlations track with MDR, they do not suggest a simple mechanism for the role of... 

The dramatic increase in terpene formation, accumulation, and emission in P. abies in response to methyl jasmonate is consistent with the effect of methyl jasmonate or jasmonic acid on many defense compounds in angiosperms. In conifers, jasmonates had been previously shown to promote the formation of heat shock and defense signaling proteins, to enhance resistance to pathogenic fimgi, and to promote colonization with ectomycorrhizae. In relation to terpenes, jasmonates had been shown to promote formation of an oxygenated sesquiterpene, todomatuic acid, and an oxygenated diterpene, paclitaxel (taxol), in cell cultures, but had never before been reported to enhance terpene accumulation in intact plants. 

The epoxide 4.2.1.2 proved resistant to nucleophilic attack, but the diol 4.2.1.1 could be converted into a number of new analogs. These included simple analogs such as various C-6 acyl derivatives 4.2.1.4 (167) but also various derivatives produced by deoxygenation at C-7. Thus diol 4.2.1.1 could be protected as its 2 -(triethylsilyl)ether, converted to its cyclic 6,7-a-thiocarbonate, and deoxygenated to the 7-deoxyanalog 4.2.I.5. Analog 4.2.1.5 can be oxidized to the ketone 4.2.1.6, which can then be reduced to the /5-alcohol 4.2.1.7 (176). Both compounds 4.2.1.5 and 4.2.1.7 were as active as taxol in a tubulin-assembly assay, but were 4 and 10 times less potent than taxol in a cytotoxicity assay with the HCT-116 human colon tumor cell line (176). 

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