The 48th FEBS Congress, Milan, İtalya, 29 Haziran - 03 Temmuz 2024, ss.318
Cellular senescence is a permanent arrest of the cell cycle in response to many stress factors and is characterized by excessive secretory activity called senescenceassociated secretory phenotype (SASP). Studies have shown that senescent cells have paracrine protumorigenic effects on the cancer microenvironment via SASP. Therefore, developing new treatment methods in cancer targeting SASP has recently become important. However, understanding how senescence contributes to cancer is difficult due to the absence of standardized SASP markers. IL6 is defined as a hallmark marker of SASP, consistently exhibiting increased expression in normal senescent cells. It has been demonstrated that cardiotrophin 1 (CTF1), a member of the IL6 family, secreted from breast cancer cells has a role in cancer metastasis. In this study, we induced senescence by incubating three different cancer cell lines, MCF7, A549, and HeLa with doxorubicin and analyzed senescent cell secretome for IL6 and CTF1. The treatment of cells with 300 nM doxorubicin significantly increased the number of senescenceassociated betagalactosidase positive cells indicating doxorubicin induced senescence in all three cell lines. In studies where we analyzed the secretome content, while the secretion of IL6 increased in senescent HeLa and A549 cells, IL6 could not be detected in the secretome of senescent MCF7 cells. On the contrary to this finding, CTF1 secretion increased in senescent MCF7 cells, while CTF1 level could not be measured in the secretome of senescent HeLa and A549 cells. It was also found that CTF1 expression increased in senescent MCF7 cells. CTF1 expression was detected in senescent HeLa and A549 cells, but no change was found in senescent cells compared to the control group. Taken together these findings indicate that IL6 cannot be considered as a SASP marker for every senescent cell and that CTF1 can be considered as a novel SASP marker for senescent MCF7 cells.