Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Induction of Senescent-Like Growth Arrest as a New Target in Anticancer Treatment

Author(s): Xianghong Wang, Sai-Wah Tsao, Yong-Chuan Wong, Annie L.M. Cheung.

Abstract:

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 β-galactosidase (β-gal) and show a permanent cell cycle G1 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 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 independent of cell cycle distribution, telomere length or cell cycle inhibitors. These observations suggest that induction of senescentlike 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 β-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.

Keywords: Senescent, chemotherapeutic drugs, anti-cancer drugs, chemodrug

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Article Details

VOLUME: 3
ISSUE: 2
Year: 2003
Page: [153 - 159]
Pages: 7
DOI: 10.2174/1568009033482001
Price: $58