Abstract 2024: Studying the effects of interfering with doxorubicin-induced senescence in human colon cancer HCT116 cells

Abstract Colorectal cancer (CRC) is type of cancer that growing in the colon or the rectum. Although CRC can be treated and managed through several means of therapy, the disease mortality is still high in Saudi Arabia. Upon treatment, cancer cells undergo different form of cell death or growth arrest such as apoptosis and senescence. Senescence is a state of proliferation arrest that is considered as a cause of drug resistance. The current study was designed to interfere with Doxorubicin-induced senescence in cancer cells, and shift the cytotoxicity of doxorubicin from proliferation arrest to apoptosis. β-galactosidase (β-gal) staining has demonstrated that Doxorubicin induces senescence in wild-type HCT116 but not in p21 knock-out cells. (DAPI)/TUNEL stating and Annexin V assay indicate that treatment with Doxorubicin promotes apoptosis in p21 knock-out HCT116 significantly more than in wild-type HCT116. β-galactosidase staining and 5-Dodecanoylaminofluorescein Di-β-D-Galactopyranosid (C12FDG) demonstrated that combination of Doxorubicin with Sorafenib, Rapamycin, or Venetoclax has significantly reduced senescence and induced more apoptosis as shown by Propidium iodide (PI)/Annexin v assay and Caspase 3/7 Assay. PCR data analysis demonstrated that not all combination of Doxorubicin with other agents significantly decreased expression of senescence protein, however, the results of this study provide findings that interference with senescence pathways may shift cytotoxicity from senescence to apoptosis. The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for partly funding this work through the project number (DRI-KSU-1273). Citation Format: Moureq Rashed Alotaibi, Homood As Sobeia, Munirah Alohaydib, Faten Alaqil, Khalid Alhazzani, Ali Alhoshani, Tareq Saleh, David Gewirtz. Studying the effects of interfering with doxorubicin-induced senescence in human colon cancer HCT116 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2024.