Programmed cell suicide is particularly important in the ovaries, where thousands of cells in the follicle should die each month, releasing just one mature egg. Failure of these cells to die on schedule causes problems ranging from infertility to cysts or ovarian cancer. Prof. Abraham Amsterdam of the Department of Molecular Cell Biology studies the role of cell suicide in both normal and cancerous ovarian cells. He has developed a method to keep granulosa cells, which make up the bulk of the ovarian follicle, alive and multiplying in the test tube, where they can be studied efficiently.
Prof. Amsterdam's team has recently discovered that glucocorticoids (hormones such as cortisol and cortisone) and leptin, a substance secreted by fat cells, protect ovarian cells from apoptosis. Both types of substances probably exert their effect through a central behind-the-scenes mediator, the BCL-2 gene, which apparently can suppress apoptosis. "Our primary goal is to learn how to fine-tune ovarian cell death," says Prof. Amsterdam. "The ability to induce apoptosis may lead to future treatments for ovarian cancer." Prof. Amsterdam's laboratory is also studying the effect of common ovarian cancer drugs, such as cisplatin and gemcitabine HCl, on apoptosis in normal and cancerous ovarian cells, and is developing new methods for the early diagnosis of ovarian cancer.
Recent research in Prof. Amsterdam's laboratory has revealed that theophylline, a widely used asthma drug, makes ovarian and lung cancer cells more vulnerable to such common anticancer medications as cisplatin and gemcitabine HCl. Apparently, theophylline helps induce massive programmed death in the cancer cells. Therefore, by giving theophylline together with common cancer drugs, it may be possible to use the cancer drugs at lower concentrations and so minimize their harmful side effects. Clinical trials in which theophylline is administered to lung cancer patients in combination with cisplatin and gemcitabine HCl are under way at the Tel Aviv Sourasky Medical Center.
