Identification of PARP-1 in cancer stem cells of gastrointestinal cancers: A preliminary study

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). Howe...

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Bibliographic Details
Published in:Journal of biosciences 2021-12, Vol.46 (1), Article 6
Main Authors: Quiñonero, Francisco, Cepero, Ana, Urbano, David, Muñoz-Gámez, José A., Martín-Guerrero, Sandra M., Martín-Oliva, David, Prados, Jose, Melguizo, Consolación, Ortiz, Raul
Format: Article
Language:English
Subjects:
5-Fluorouracil
Adenosine
Adenosine diphosphate
ADP
Apoptosis
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer therapies
Cell Biology
Chemotherapy
Colon
Colon cancer
Colorectal cancer
Cytotoxicity
Damage
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
Doxorubicin
Gastrointestinal cancer
Gemcitabine
Hepatocytes
Inhibitors
Irinotecan
Life Sciences
Liver
Liver cancer
Metastases
Microbiology
Neoplasms
Pancreas
Pancreatic cancer
Plant Sciences
Poly(ADP-ribose) polymerase
Resistance mechanisms
Ribose
Stem cells
Technology assessment
Tumor cell lines
Tumor cells
Tumors
Zoology
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Summary: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.
ISSN:0250-5991
0973-7138
DOI:10.1007/s12038-020-00135-1