Cytotoxic/protective activity tumor cells

Fig. 7.1 Schematic representation of the cytotoxic/protective roles of NO in cancer. The complicated outcome of cytotoxic/protective activity of NO depends on the concentration of NO and microenvironment with tumor cells and tumor-associated macrophages. High concentrations of NO, principally induced by iNOS, may induce anti-cancer effects in tumor cells, whereas low, but continuous, concentrations of NO, mainly induced by eNOS, may result in pro-cancer effects. NO has also the potential to enhance both radiotherapy and chemotherapy...

Recently it was demonstrated that transfection of tumor cells with an antitumor peptide induced a protective immune reponse. Inoculation of mice with murine BD-2-transfected leukemia cells enhanced cytotoxic T lymphoc)des (CTL) and natural killer (NK) anti-tumor activity, with augmented IL-12 and IFN-y production. Animals vaccinated with transfected cells were protected against a challenge with parental cells (50% protection) and the vaccination generated leukemia-specific memory CTL [210]. 

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). 

Low cell proliferation rates and cell cycle arrest distant from tumor microvessels can protect tumor cells from the effects of cytotoxic therapies whose activity is selective for rapidly dividing cell populations. 

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