Programmed for death
Programmed for death
Cells are not immortal. But cancer scientists have only recently taken this fact seriously. Apoptosis, a Greek word meaning the shedding of leaves in autumn, refers to the tendency of cells to commit suicide. Billions of cells kill themselves every hour as other cells proliferate continuously to maintain a constant cell count. Why would cells want to die? How do they die? Can cancer be cured by inducing apoptosis?
Normally, cells face natural death, except in a phenomenon called necrosis, where untimely death is caused by external factors like poison, excessive heat or insufficient oxygen. For decades, researchers have killed cells using poisons, radiation and surgery. Necrosis is quite messy, with membrane rupture and the spilling of cell chemicals that damage surrounding tissue.
When a cell is set to kill itself, it first prepares the weaponry - enzymes. The suicide genes then order the celt to assume a peculiar shape while the enzymes cut up the cell contents into pieces that can be eaten up by neighbouring cells. After the cells start breaking up, phagocytes, which are the body's janitors, clean up the garbage.
Martin Raff, professor of biology at University College, London, says that all living cells are genetically programmed to kill themselves and that a cell isolated from its environment dies of apoptosis immediately. Raff's experiments with brain cells showed that cells require substances like cytokines and growth factors produced by the surrounding cells to survive.
Corroborating Raff's theory, Gerard Evans, head of the Imperial Cancer Research Fund in London, found that the C-MYC gene works as a switch for apoptosis. If the gene is turned on, the cell proliferates; otherwise, the cell kills itself. Says Evans, "You need C-MYC to become a tumour but switching on C-MYC kills you." In all types of cancer, the mutant form of C-MYC that cannot be turned off is present.
Evans' work also establishes the link between this gene and cytokines, without which the gene cannot function. Cytokines have 2 sets of growth factors - one turns on cell growth but also instructs self-destruction, whereas the second, called insulin-like growth factor (IGF-1), overrides the apoptosis instruction.
Scientists have been looking at IGF-1 for targeting as a drug. There are other genes like MTS1, which coordinate the activities of C-MYC in apoptosis. In most human cancers, the functional copies of MTS1 are missing, leaving C-MYC on forever. Researchers hope to use it as a drug to induce apoptosis.