DNA-damaging Agents-induced Formation Of Senescence-associated Heterochromatic Foci (SAHF) In Tumor Cells

With the acceleration of aging process in human society, Senescence has been subjectedto extensive concern in recent years. Cellular senescence, a growth-arrest program that limitsthe lifespan of mammalian cells and prevents unlimited cell proliferation, is attractingconsiderable interest because of its links to tumour suppression. At the cellular level,senescence means irreversibly loss of proliferative potential and entering a relatively stablestate. Senescent cells usually arrest in the cell cycle of G1phase with a series ofmorphological and physiological alterations including a flat and enlarged morphology, anincrease in acidic beta-galactosidase activity and significantly reduced cell proliferationability. At the level of chromatin, senescence is accompanied by extensive changes inchromatin structure. In particular, many senescent cells accumulate specialized domains offacultative heterochromatin, called Senescence-Associated Heterochromatin Foci (SAHF),which are thought to repress expression of proliferation-promoting genes, therebycontributing to senescence-associated proliferation arrest. Primary human fibroblastsundergoing oncogene-induced or replicative senescence are known to form senescence-associated heterochromatin foci (SAHF), which contribute to the stability of the senescentstate. However, it is unclear whether SAHF formation is universal in tumor cells. Moreover,how the SAHF assembly pathway is activated in senescent cells is not fully understood.DNA-damaging agents are able to induce irreversible cell growth arrest and senescence insome types of tumor cells, thus contributing to the static feature of tumor. DNA-damagingagents are able to induce irreversible cell growth arrest and senescence in some types oftumor cells, thus contributing to the static feature of tumor. However, senescent tumor cellsmay re-enter the cell cycle leading to tumor relapse. Understanding the mechanisms thatcontrol the viability of senescent cells may be critical for tumor suppression. We use twokinds of the DNA damaging agents doxorubicin (Dox) and7-Ethyl-10-hydroxy-camptothecin(SN-38) to induce cell senescence in some tumor cell types. Here we report that the DNAdamaging agents were able to induce the formation of SAHF in some tumor cell types, forMDA-MB-231and MDA-MB-435cell lines; however, some tumor cell types were unable toform SAHF when treated with DNA damaging agents. SAHF formation is not a generalphenomenon among tumor cells, for its occurrence is largely cell lineage-dependent. Thesedata establishes the foundation for investigating the mechanisms that control the formation ofSAHF in tumor cells.