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      https://www.ias.ac.in/article/fulltext/jbsc/045/0121

    • Keywords

       

      Cancer stem cells; CD133; colorectal cancer; 5-fluorouracil; MGMT; MMR

    • Abstract

       

      Cancer stem cells (CSCs) from colorectal cancer (CRC), characterized by CD133 expression, have beenassociated with 5-fluorouracile (5-FU) chemoresistance. DNA repair mechanisms, such as O6-alkylguanineDNA alkyltransferase (MGMT) and mismatch repair (MMR) systems, have also been correlated to 5-FUresistance in CRC. The aim of this study was to evaluate the modulation of CD133 and MGMT in MMRproficientand MMR-deficient CRC cells under 5-FU treatment and the effect of this drug in CSCs. CD133 andMGMT methylation status were determined in MMR-proficient (SW480 and HT29) and MMR-deficient (RKOand HCT116) cell lines by methylation-specific PCRs. SW480 and RKO were selected to determine modulationof CD133, MGMT and MMR expression after 5-FU treatment by qPCR. In addition, CD133, MGMTand MMR were analyze in SW480 and RKO CSCs. No association between promoter methylation and MGMTand CD133 expression was found. 5-FU treatment increased CD133 expression independently to MMR statusin SW480 and RKO and was able to increase hMLH1 expression in RKO, a MMR-deficient cell line. RKO/CSCs overexpressed CD133 and MMR (hMSH2 and hMSH6) while SW480/CSCs showed a significantincrease in CD133, MMR (hMLH1, hMSH2 and hMSH6) and MGMT, moreover 5-FU resistance thanparental cell lines. Thus, although CSCs 5-FU chemoresistance appears to be independently to MMR status,hMLH1 might play a key role in CSC response to 5-FU. New drugs exploding these differences could benefitthe prognostic of patients with CRC.

    • Author Affiliations

       

      JAIME A OLIVER1 2 RAU´L ORTIZ2 3 4 CRISTINA JIME´NEZ-LUNA2 3 5 LAURA CABEZA2 3 4 GLORIA PERAZZOLI2 4 6 OCTAVIO CABA2 3 4 CRISTINA MESAS2 3 4 CONSOLACIO´N MELGUIZO2 3 4 JOSE PRADOS2 3 4

      1. Center for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
      2. Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
      3. Department of Anatomy and Embryology, University of Granada, Granada, Spain
      4. Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain
      5. Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland
      6. Department of Medicine, University of Almeria, 04120 Almerı´a, Spain
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