Induction of senescent-like growth arrest as a new target in anticancer treatment.
Replicative senescence is a programmed cellular response in normal cells, the induction of which depends on the accumulated number of cell divisions. Unlike cells undergoing apoptosis, senescent cells have a large and flat morphology, express acidic beta-galactosidase (beta-gal) and show a permanent cell cycle G(1) phase arrest. Recently, senescent-like growth arrest has been observed in many types of tumor cell lines after exposure to certain chemotherapeutic drugs. These senescent-like cancer cells show similar morphology, growth arrest and beta-gal expression to normal cells undergoing replicative senescence. However, unlike replicative senescence during the aging process, the chemodrug-induced senescent-like growth arrest is independent of cell cycle distribution, telomere length or cell cycle inhibitors. These observations suggest that induction of senescent-like response may provide a novel target leading to permanent growth arrest in cancer cells. So far, cell lines derived from more than 14 types of cancers have shown senescent-like growth arrest by either introduction of tumor suppressor genes or treatment with chemotherapeutic drugs. In addition, the drug-induced beta-gal expression has been correlated with cancer cells undergoing terminal senescent-like growth arrest, which provides a possible marker for this process. This review will describe the evidence on senescent-like growth arrest in human cancer cells and the molecular changes that differ between chemodrug-induced 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 anti-cancer drugs are addressed.
Wang
Xianghong
X
Cancer Biology Laboratory, Department of Anatomy, Faculty of Medicine, University of Hong Kong, 21 Sassoon Road, Hong Kong, China. xhwang@hkucc.hku.hk
Tsao
Sai-Wah
SW
Wong
Yong-Chuan
YC
Cheung
Annie L M
AL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D006801:Humans
D000970:Antineoplastic Agents