Cell division and apoptosis

The final mitosis stage involves separation of two sets of chromosomes via microtubules that are filamentous polymers of tubulin monomers. Compounds that interfere with tubulin polymerization such as the plant-derived compounds colchicine, taxol, vinblastine and vincristine are cell division inhibitors (Table 9.6). The cytokinesis of the daughter cells requires equal division of cytoplasm and an actin-myosin-based contractile ring provides the force to make this separation. Accordingly, compounds such as cytochalasin B that interfere with actin will also interfere with cell division (Table 9.6). 

Apoptosis or programmed cell death is a highly regulated process required in developmental events such as embryological tissue remodelling and the endometrial changes of the menstrual cycle. The cell complement in particular tissues of metazoans derives from a balance between apoptosis and cell division and an imbalance in favour of cell multiplication is associated with cancer. 

Apoptosis in viral-infected cells is induced by cytotoxic T( cells bound (via both the cell surface T cell receptor and CD8 protein) to the target cell MHCI complex (which presents a virus-derived peptide). This process is assisted by interleukin-2 (IL-2) (acting via the PM IL-2 receptor on T( cells), the IL-2 having been generated by helper TH cells complexed (via both the cell surface T cell receptor and CD4 protein) to a macrophage MHCII complex 

Signalling for apoptosis can involve a plasma Fas ligand which binds to the PM Fas receptor with resultant activation of an associated cytosol-side Fas death domain of Fas and activation of caspase 8. Caspase 8 is a thiol protease and once activated initiates a so-called caspase cascade leading to activation of further caspases (with consequent proteolysis) and activation of a DNase (leading to DNA destruction with formation of a characteristic DNA fragment ladder ). Caspase 8 acts on mitochondria with resultant release of cytochrome c, which promotes caspase 3 activation by caspase 8 and hence the caspase cascade . Another signalling pathway for apoptosis involves tumour necrosis factor (TNF) binding to the TNF receptor with consequent activation of a cytosolic-side TNF receptor-associated death domain (TRADD) and resultant activation of the caspase cascade and cell death. 

A large number of plant-derived compounds are apoptotic., having been variously shown to activate caspases, cause membrane blebbing or induce formation of a ladder of fragmented DNA. Such compounds are cytotoxic and have potential as anti-neoplastic agents (Table 9.7). 

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