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AuthorNaji, Sara
AuthorIssa, Khodr
AuthorEid, Assaad
AuthorIratni, Rabah
AuthorEid, Ali H.
Available date2020-08-18T08:34:17Z
Publication Date2019
Publication NameCellular Physiology and Biochemistry
AbstractBackground/Aims: Cadmium (Cd) is a heavy metal contaminant whose toxicity is associated with colorectal cancer (CRC). However, the underlying molecular mechanisms of Cd-induced CRC malignancy remain obscure. Methods: A monolayer scratch assay was employed to assess the migration of HT-29 human adenocarcinoma cells. Luciferase reporter assay was used to determine cyclooxygenase-2 (COX-2) transcriptional activity, and Western blotting was used to detect p38 Mitogen Activated Protein Kinase (MAPK) and Akt phosphorylation as well as COX-2 expression. Prostaglandin E2 (PGE2) levels were measured using Enzyme Linked Immunosorbent Assay (ELISA) and reactive oxygen species (ROS) formation was assessed using dihydroethidium (DHE) stain. Results: Here, we show that Cd potentiates the migratory capacity of HT-29 CRC cells. Cd caused a time-dependent increase in COX-2 expression. Celecoxib, a COX-2 selective inhibitor, significantly reduced Cd-induced migration. Cd also increased levels of ROS and phosphorylated p38. Importantly, Cd-induced COX-2 expression and migration were significantly abolished by N-Acetyl-Cysteine (NAC), a ROS scavenger, or SB202190, a specific p38 inhibitor. Furthermore, Cd-induced p38 phosphorylation was inhibited by NAC. Cd (100 nM) also increased PGE2 levels, which was abrogated by NAC, SB202190, or celecoxib. Exogenous PGE2 significantly potentiated cell migration. Cd caused a significant increase in Akt phosphorylation in a ROS-mediated pathway. Moreover, Cd-induced migration was significantly attenuated by LY294 002, a phosphatidylinositol-3-kinase inhibitor. Conclusion: Taken together, our results suggest that exposure to low levels of Cd promotes a more migratory cancer phenotype in a ROS-p38-COX-2-PGE2 pathway as well as ROS-Akt pathway. Therefore, COX-2, PGE2 receptors or Akt represent potential targets in the treatment of CRC, particularly in patients exposed to Cd. - 2019 The Author(s). Published by Cell Physiol Biochem Press GmbH&Co. KG
PublisherCell Physiol Biochem Press GmbH & Co KG
SubjectColorectal cancer
SubjectEnvironmental pollution
TitleCadmium induces migration of colon cancer cells: Roles of reactive oxygen species, p38 and cyclooxygenase-2
Issue Number6
Volume Number52

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