Molecular Mechanisms of Prostate Cancer Cell Death Triggered by Inhibition of Arachidonate 5-Lipoxygenase: Involvement of Fas Death Receptor-Mediated Signals

Abstract

Cancer is the result of uncontrolled cell proliferation and has emerged as one of the most frequently diagnosed challenges to human health all over the world. While formation of new cells is an integral part of cancer biology, decreased death of tumor cells has recently emerged as a focus of attention as the leading cause of deregulated tissue homeostasis resulting in cancer-related tumor burden. The cell loss factor is the major determinant of tumor growth rate with values approaching to as high as 90% in some case (1). Chemotherapeutic drugs are designed to reverse the order of cancer cell behavior by blocking cell division and/or increasing cell death. Apoptosis, or programmed cell death, is a genetically based suicide mechanism preserved through evolutionary ages (2), by which infected and damaged cells are selectively eliminated from the body in a controlled fashion without much inflammatory or bystander effects. It is the dominant mechanism of cell death in multicellular species. Drugs currently in use for cancer chemotherapy, in most cases, work by induction of apoptosis, either through membrane-localized cell death receptor-mediated signals or by the involvement of mitochondria. Other cancer-therapeutic modalities including radiotherapy, immunotherapy and hormone ablation also induce cell death by apoptosis. Tumor cells, on the other hand, are posing a threat of drug-resistance by deregulating the cell-death program (“drug neo-resistance”) or immuno-resistance by expressing cell death signal-inducing ligands on their surface to counterattack the antitumor lymphocytes.