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      https://www.ias.ac.in/article/fulltext/jbsc/046/0006

    • Keywords

       

      Cancer stem cells; colon cancer; liver cancer; Olaparib; pancreatic cancer; PARP-1

    • Abstract

       

      Advanced-stage gastrointestinal tumors have high mortality due to chemotherapy limitations. One of thecauses of treatment failure is the presence of cancer stem cells (CSCs), which show resistance mechanismsagainst DNA damage, such as poly (adenosine diphosphate-ribose) polymerase 1 (PARP-1). However, little isknown about the relevance of PARP-1 in these tumor cells. Our purpose is to analyze the expression of PARP-1in cancer cells and CSCs from gastrointestinal tumors, its relationship with the DNA damage repair processand its modulation by cytotoxic and PARP-1 inhibitors. We used pancreatic, liver and colon cancer cell linesand isolated CSCs using Aldefluor technology to analyze PARP-1 expression. In addition, we examined theeffect of classic cytotoxic drugs (Doxorubicin, Gemcitabine, Irinotecan and 5-Fluorouracil) and a PARP-1inhibitor (Olaparib) in cultured cells and 3D tumorspheres. We demonstrated that PARP-1 is highly expressedin pancreatic, liver and colon tumor cells and that this expression was significantly higher in cell populationswith CSC characteristics. In addition, Doxorubicin and Gemcitabine increased their cytotoxic effect whenadministered simultaneously with Olaparib, decreasing the formation of 3D tumorspheres. Our findings suggestthat PARP-1 is a common and relevant resistance mechanism in CSCs from gastrointestinal tumors andthat the use of PARP-1 inhibitors may be an adjuvant therapy to increase apoptosis in this type of cells whichare responsible to cancer recurrence and metastasis.

    • Author Affiliations

       

      QUIN˜ONERO1 2 3 ANA CEPERO1 2 DAVID URBANO1 JOSE´ A MUN˜ OZ-GA´ MEZ4 SANDRA M MARTI´N-GUERRERO5 DAVID MARTI´N-OLIVA5 JOSE PRADOS1 2 3 CONSOLACIO´ N MELGUIZO1 2 3 RAUL ORTIZ1 2 3

      1. Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
      2. Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
      3. Instituto de Investigacio´n Biosanitaria ibs.GRANADA, 18012 Granada, Spain
      4. BD Biosciences, 28750 Madrid, Spain
      5. Department of Cellular Biology, Science Faculty, University of Granada, 18071 Granada, Spain
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