Akademik Veri Yönetim Sistemi
3rd International Gazi Pharma Symposium Series, Ankara, Türkiye, 8 - 10 Eylül 2021
Cellular senescence is induced in cancer cells in response to chemotherapeutics at low concentrations that do not stimulate cell death. Although senescent cancer cells are not able to proliferate, they cause various negative pro-tumorigenic paracrine effects on the cells in the cancer microenvironment with the various factors they secrete called senescence-associated secretory phenotype (SASP). Thus developing senotherapeutic drugs that kill senescent cells and inhibit the secretory activity of senescent cancer cells is a new approach in cancer therapy. The current work evaluated the possible role of theophylline in doxorubicin-induced senescence and senescent cell morphology in A549 cells. We demonstrated that while incubation of doxorubicin significantly induced SA-β-gal-positive cancer cells, the proportion of cells positive for SA-β-gal increased after the pre-incubation of theophylline. In addition, a significant reduction in senescent cell area was observed after theophylline pre-incubation. Changes in cell shape and morphology modulate cell function in biological organisms. Senescent cell form and secretory function are also closely related. In the current study, the decrease in cell morphology caused by theophylline may result in a decrease in the secretory activity of the senescent cell. Therefore, with the potential senotherapeutic activity of theophylline, undesirable effects caused by the secreted factors of senescent cancer cells can be eliminated. Our ongoing studies investigating the effect of theophylline on the secretory activity of the senescent cancer cell will provide additional evidence for the senotherapeutic efficacy of this compound.
This study was supported by the Scientific Project Unit of Gazi University (Grant code:
02/2020-07).
Keywords: Senescence, SASP, cancer, theophylline