Induction of Tumour Cell Senescence: A New Strategy in Anticancer Treatment

Abstract

Replicative senescence is a programmed cellular response in normal cells, the induction of which depends on the accumulated number of cell divisions. Recently, senescent-like growth arrest has been observed in many types of human tumour cell lines after exposure to a number of chemotherapeutic drugs. These senescent-like cancer cells show similar morphology, growth arrest and β-gal expression to normal cells undergoing replicative senescence. However, unlike replicative senescence during the aging process, the chemodrug-induced senescent-like growth arrest is not entirely dependent of cell cycle distribution, telomere length or cell cycle inhibitors. These observations suggest that induction of senescent-like response may provide a novel strategy leading to permanent growth arrest in cancer cells. So far cell lines derived from more than 20 types of cancers have shown senescent-like growth arrest by either introduction of tumour suppressor genes or treatment with chemotherapeutic drugs, and increased β-gal expression has been correlated with cancer cells undergoing terminal senescent-like growth arrest. In addition, the recent demonstration that cancer cell senescence was observed in both animal models and human frozen specimens after exposure to anticancer drugs, which was also associated with β-gal expression and treatment outcome, indicates that tumour senescence may not only provide an alternative target for the treatment of human cancer but also a prognostic indicator. This review will describe the evidence on senescent-like growth arrest in human cancer cells and the molecular changes that differ between chemodruginduced senescent-like growth arrest and apoptosis. In addition, the possible factors and mechanisms involved in this process are also discussed. Finally, the implications on how senescent-like growth arrest might be exploited as a possible new target for the development of new anti-cancer drugs are addressed. Keywords: senescent-like growth arrest, anticancer treatment