@misc{10481/102649,
year = {2021},
month = {2},
url = {https://hdl.handle.net/10481/102649},
abstract = {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},
organization = {This work was supported by funds from group CTS107 (Andalusian Government). FQ acknowledges the FPU2018 grant from the Ministerio de Educación, Ciencia y Deporte y Competitividad (Spain). We are
grateful for the help provided by Dr. Gustavo Ortiz Ferrón in answering some of the questions raised by the reviewers on cytometry.},
publisher = {Springer Nature},
keywords = {cancer stem cells},
keywords = {colon cancer},
keywords = {liver cancer},
keywords = {Olaparib},
keywords = {pancreatic cancer},
keywords = {PARP-1},
title = {Identification of PARP-1 in cancer stem cells of gastrointestinal cancers: a preliminary study},
doi = {10.1007/s12038-020-00135-1},
author = {Quiñonero Muñoz, Francisco José and Cepero, Ana and Urbano, David and Muñoz-Gámez, José Antonio and Martín-Guerrero, Sandra María and Martín Oliva, Francisco David and Prados Salazar, José Carlos and Melguizo Alonso, Consolación and Ortiz Quesada, Raúl},
}