Cellular senescence is a physiological program of terminal growth arrest that can be triggered by alteration of telomeres or by different forms of stress. Senescent cells can not divide even upon mitogen stimulation, but they remain metabolically active and show characteristic changes in morphology such as enlarged and flatten cell shape and increased granularity. Based on the in vitro and in vivo experiments, induction of cellular senescence was shown to play an important role in suppressing tumorigenesis in mouse and human. During the process of carcinogenesis only the cells that are able to bypass cellular senescence acquire fully transformed phenotype. It has now become apparent however, that tumor cells can be forced to undergo senescence by genetic manipulations or by treatment with chemotherapeutic drugs, radiation or differentiating agents. Since cellular senescence leads to inhibition of cancer cells proliferation, it seems to be an attractive approach to anti-cancer therapy. Based on our own experiments we were able to show that treatment of HCT116 human colon cancer cell line with low dose of doxorubicin leads to induction of cellular senescence characterized by morphological and biochemical changes typical for this process like enlargement of cells, induction of p53 and p21 proteins and increased activity of SA-β-galactosidase. Moreover, DNA content analysis revealed that drug-induced senescence of colon cancer cells was correlated with polyploidisation. Although the majority of polyploid cells acquired senescent phenotype few days after doxorubicin treatment, we simultaneously observed rare events of aberrant mitotic cell division of some polyploid cells. The process of defective mitosis gave rise to aneuploid progeny as confirmed by chromosomal spreads analysis. What seems to be particularly important, those aneuploid cells gain the ability to proliferate leading to overgrowth of the population of undividing, senescent cell. Thus we can conclude that induction of HCT116 colon cancer cell senescence is correlated with induction of genetic instability, which can contribute to tumor development thus questioning cancer cell senescence as a promising anti-cancer therapy.

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1. New isothiazolopyridines and their in vitro antibacterial activity
2. Aneuploidy and cancer; Bcr-Abl expression leads to compromised mitotic spindle checkpoint promoting chromosomal instability