PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis
Version 1
: Received: 27 May 2023 / Approved: 30 May 2023 / Online: 30 May 2023 (04:02:57 CEST)
How to cite:
Sharif, E.; Mandegary, A.; Hassanzadeh, A. Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis. Preprints2023, 2023052032. https://doi.org/10.20944/preprints202305.2032.v1
Sharif, E.; Mandegary, A.; Hassanzadeh, A. Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis. Preprints 2023, 2023052032. https://doi.org/10.20944/preprints202305.2032.v1
Sharif, E.; Mandegary, A.; Hassanzadeh, A. Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis. Preprints2023, 2023052032. https://doi.org/10.20944/preprints202305.2032.v1
APA Style
Sharif, E., Mandegary, A., & Hassanzadeh, A. (2023). Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis. Preprints. https://doi.org/10.20944/preprints202305.2032.v1
Chicago/Turabian Style
Sharif, E., Ali Mandegary and Abdolreza Hassanzadeh. 2023 "Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis" Preprints. https://doi.org/10.20944/preprints202305.2032.v1
Abstract
Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. Accumulating clinical and experimental evidence suggests the role of cyclo-oxygenase (COX) enzymes in the pathogenesis of cancers including HCC. Deuterium-enriched water (DEW) and deuterium-depleted water (DDW) play a role both in the treatment and prevention of cancers. Combination therapy using COX-inhibitors and DDW/DEW could be a rational strategy to enhance the cytotoxicity of either agent in HCC. The cytotoxicity of celecoxib or indomethacin, alone and in combination with DDW or DEW was determined in the Hep-G2 HCC cell line by MTT assay. The COX-2, MAPK pathway proteins, the anti-apoptotic Bcl2 and pro-apoptotic Bax proteins, and caspase-3 activity were determined by SDS-PAGE and western blot. Co-treatment of selective and non-selective COX-2 inhibitors with DEW led to a remarkable increase in cytotoxicity and apoptosis of Hep-G2 cells. These events were associated with the activation of p38 and JNK MAPKs and a decrease in pro-survival proteins Bcl-2, COX-2, and ERK1/2. Furthermore, the combination therapy activated caspase-3, and the apoptosis mediator, and disabled poly ADP-ribose polymerase (PARP), the key DNA repair enzyme, by cleaving it. The combination of DEW with NSAIDs might be effective against HCC cells by influencing principal cell signaling pathways, and this has a potential to become a candidate for chemotherapy.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
