CYCLOOXYGENASE INHIBITORS COMBINED WITH DEUTERIUM-ENRICHED WATER AUGMENT CYTOTOXICITY IN A549 LUNG CANCER CELL LINE VIA ACTIVATION OF APOPTOSIS AND MAPK PATHWAYS

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HASSANZADE ABDOLREZA; MANDEGARY ALI; SHARIF ELHAM; RASOULI ROKHSANA; MOHAMMADNEJAD REZA; MASOUMI ARDAKANI YASER

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Journal: Iranian Journal of Basic Medical Sciences Year:2018 | Volume:21 | Issue:5 Page(s): 508-516

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Title

CYCLOOXYGENASE INHIBITORS COMBINED WITH DEUTERIUM-ENRICHED WATER AUGMENT CYTOTOXICITY IN A549 LUNG CANCER CELL LINE VIA ACTIVATION OF APOPTOSIS AND MAPK PATHWAYS

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Keywords

A549 LUNG CANCER CELL

APOPTOSIS

COMBINATION THERAPY

CYCLOOXYGENASE INHIBITORS

DEUTERIUM ENRICHED WATER

MAPK PATHWAY

Abstract

Objective (s): Combination chemotherapy is a rational strategy to increase patient response and tolerability and to decrease adverse effects and drug resistance. Recently, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to be associated with reduction in occurrence of a variety of cancers including lung cancer. On the other hand, growing evidences suggest that deuterium-enriched water (DEW, D2O) and deuterium-depleted water (DDW) play a role both in treatment and prevention of cancers. In the present study, we examined the effects of DEW and DDW in combination with two NSAIDs, celecoxib and indomethacin, on A549 human non-small lung cancer cell to identify novel treatment options.Materials and Methods: The cytotoxicity of celecoxib or indomethacin, alone and in combination with DDW and DEW was determined. The COX-2, MAPK PATHWAY proteins, the anti-apoptotic Bcl2 and pro-apoptotic Bax proteins and caspase-3 activity were studied for cytotoxic combinations.Results: Co-administration of selective and non-selective COX-2 inhibitors with DEW led to a remarkable increase in cytotoxicity and APOPTOSIS of A549 cells. These events were associated with activation of p38 and JNK MAPKs and decreasing 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.Conclusion: The combination of DEW with NSAIDs might be effective against lung cancer cells by influence on principal cell signalling pathways, and this has a potential to become a candidate for chemotherapy.

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APA: Copy

HASSANZADE, ABDOLREZA, MANDEGARY, ALI, SHARIF, ELHAM, RASOULI, ROKHSANA, MOHAMMADNEJAD, REZA, & MASOUMI ARDAKANI, YASER. (2018). CYCLOOXYGENASE INHIBITORS COMBINED WITH DEUTERIUM-ENRICHED WATER AUGMENT CYTOTOXICITY IN A549 LUNG CANCER CELL LINE VIA ACTIVATION OF APOPTOSIS AND MAPK PATHWAYS. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, 21(5), 508-516. SID. https://sid.ir/paper/706513/en

Vancouver: Copy

HASSANZADE ABDOLREZA, MANDEGARY ALI, SHARIF ELHAM, RASOULI ROKHSANA, MOHAMMADNEJAD REZA, MASOUMI ARDAKANI YASER. CYCLOOXYGENASE INHIBITORS COMBINED WITH DEUTERIUM-ENRICHED WATER AUGMENT CYTOTOXICITY IN A549 LUNG CANCER CELL LINE VIA ACTIVATION OF APOPTOSIS AND MAPK PATHWAYS. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES[Internet]. 2018;21(5):508-516. Available from: https://sid.ir/paper/706513/en

IEEE: Copy

ABDOLREZA HASSANZADE, ALI MANDEGARY, ELHAM SHARIF, ROKHSANA RASOULI, REZA MOHAMMADNEJAD, and YASER MASOUMI ARDAKANI, “CYCLOOXYGENASE INHIBITORS COMBINED WITH DEUTERIUM-ENRICHED WATER AUGMENT CYTOTOXICITY IN A549 LUNG CANCER CELL LINE VIA ACTIVATION OF APOPTOSIS AND MAPK PATHWAYS,” IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, vol. 21, no. 5, pp. 508–516, 2018, [Online]. Available: https://sid.ir/paper/706513/en

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