PLANTS THAT FIGHT CANCER - PART 3

Các hiệu ứng sinh hóa khác có liên quan với VBL và VCR bao gồm: cạnh tranh để vận chuyển các axit amin vào tế bào, ức chế sinh tổng hợp purine, sự ức chế của RNA, DNA và tổng hợp protein, ức chế glycolysis, ức chế giải phóng histamin từ tế bào mast và nâng cao phát hành của epinephrine | 52 Spiridon E. Kintzios et al. Other biochemical effects that have been associated with VBL and VCR include competition for transport of amino acids into cells inhibition of purine biosynthesis inhibition of RNA DNA and protein synthesis inhibition of glycolysis inhibition of release of histamine by mast cells and enhanced release of epinephrine and disruption in the integrity of the cell membrane and membrane functions. Microtubules are present in eukaryotic cells and are vital to the performance of many critical functions including maintenance of cell shape mitosis meiosis secretion and intracellular transport. VBL and VCR exert their antimicrotubule effects by binding to a site on tubulin that is distinctly different from the binding sites of others. They have a binding constant of X 10 5M and initiate a sequence of events that lead to disruption of microtubules. The binding of VBL and VCR to tubulin in turn prevents the polymerization of these subunits into microtubules. The net effects of these processes include the blockage of the polymerization of tubulin into microtubules which may eventually lead to the inhibition of vital cellular processes and cell death. Although most evidence suggests that mitotic arrest is the principal cytotoxic effect of the alkaloids there is also evidence that suggests that the lethal effects of these agents may be attributed in part to effects on other phases of the cell cycle. The alkaloids also appear to be cytotoxic to nonproliferating cells in vitro and in vivo in both G1 and S cell cycle phases. In other words VBL and VCR work by inhibiting mitosis in metaphase Danieli 1998 Garnier et al. 1996 . Studies with germinating seedlings have suggested that alkaloid biosynthesis and accumulation are associated with seedling development. Studies with mature plants also reveal this type of developmental control. Furthermore alkaloid biosynthesis in cell suspension cultures appears to be coordinated with cytodifferentiation. .

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