Apoptosis induction by chemopreventive agents

The goals of cancer chemoprevention are to inhibit the induction or suppress the progression of preneoplastic lesions to invasive cancer by using specific natural or synthetic chemical agents. Numerous studies have demonstrated that suppression of apoptosis or defects in apoptotic pathways contribute to expansion of initiated or aberrant clones leading to cancer development. Therefore, agents that can eliminate aberrant clones by induction of apoptosis rather than merely slowing down their proliferation may have chemopreventive potential. The increased understanding of apoptosis pathways has directed attention to components of these pathways as potential targets for not only chemotherapeutic but also chemopreventive agents. Indeed, an increasing number of previously identified chemopreventive agents including retinoids, vitamin D(3) analogues, triterpenoids, butyroids, monoterpenoids, nonsteroidal antiinflammatory agents and others were found recently to enhance apoptosis in a variety of premalignant or malignant cell types in vitro and in a few animal models in vivo and in clinical trials. Further understanding of the effects of potential chemopreventive agents on specific components of the pathways that lead to apoptosis may provide a rational approach to use such agents alone or in combination with other agents to enhance apoptosis as a strategy for effective chemoprevention of cancer.