Identification of PARP-1 in cancer stem cells of gastrointestinal cancers: a preliminary study Quiñonero Muñoz, Francisco José Cepero, Ana Urbano, David Muñoz-Gámez, José Antonio Martín-Guerrero, Sandra María Martín Oliva, Francisco David Prados Salazar, José Carlos Melguizo Alonso, Consolación Ortiz Quesada, Raúl cancer stem cells colon cancer liver cancer Olaparib pancreatic cancer PARP-1 Advanced-stage gastrointestinal tumors have high mortality due to chemotherapy limitations. One of the causes of treatment failure is the presence of cancer stem cells (CSCs), which show resistance mechanisms against DNA damage, such as poly (adenosine diphosphate-ribose) polymerase 1 (PARP-1). However, little is known about the relevance of PARP-1 in these tumor cells. Our purpose is to analyze the expression of PARP-1 in cancer cells and CSCs from gastrointestinal tumors, its relationship with the DNA damage repair process and its modulation by cytotoxic and PARP-1 inhibitors. We used pancreatic, liver and colon cancer cell lines and isolated CSCs using Aldefluor technology to analyze PARP-1 expression. In addition, we examined the effect of classic cytotoxic drugs (Doxorubicin, Gemcitabine, Irinotecan and 5-Fluorouracil) and a PARP-1 inhibitor (Olaparib) in cultured cells and 3D tumorspheres. We demonstrated that PARP-1 is highly expressed in pancreatic, liver and colon tumor cells and that this expression was significantly higher in cell populations with CSC characteristics. In addition, Doxorubicin and Gemcitabine increased their cytotoxic effect when administered simultaneously with Olaparib, decreasing the formation of 3D tumorspheres. Our findings suggest that PARP-1 is a common and relevant resistance mechanism in CSCs from gastrointestinal tumors and that the use of PARP-1 inhibitors may be an adjuvant therapy to increase apoptosis in this type of cells which are responsible to cancer recurrence and metastasis 2025-02-25T06:47:35Z 2025-02-25T06:47:35Z 2021-02-03 journal article Quinonero, F., Cepero, A., Urbano, D., Munoz-Gamez, J. A., Martin-Guerrero, S. M., Martin-Oliva, D., Prados, J., Melguizo, C., & Ortiz, R. (2021). Identification of PARP-1 in cancer stem cells of gastrointestinal cancers: A preliminary study. Journal of biosciences, 46, 6. https://hdl.handle.net/10481/102649 10.1007/s12038-020-00135-1 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Springer Nature