سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Hassanzadeh, Abdolreza, Mandegary, Ali, Sharif, Elham, Rasooli, Rokhsana, Mohammadnejad, Reza, Masoumi, Yaser. (1397). Cyclooxygenase inhibitors combined with deuterium-enriched water augment cytotoxicity in A549 lung cancer cell line via activation of apoptosis and MAPK pathways. , 21(5), 508-516. doi: 10.22038/ijbms.2018.25366.6269
Abdolreza Hassanzadeh; Ali Mandegary; Elham Sharif; Rokhsana Rasooli; Reza Mohammadnejad; Yaser Masoumi. "Cyclooxygenase inhibitors combined with deuterium-enriched water augment cytotoxicity in A549 lung cancer cell line via activation of apoptosis and MAPK pathways". , 21, 5, 1397, 508-516. doi: 10.22038/ijbms.2018.25366.6269
Hassanzadeh, Abdolreza, Mandegary, Ali, Sharif, Elham, Rasooli, Rokhsana, Mohammadnejad, Reza, Masoumi, Yaser. (1397). 'Cyclooxygenase inhibitors combined with deuterium-enriched water augment cytotoxicity in A549 lung cancer cell line via activation of apoptosis and MAPK pathways', , 21(5), pp. 508-516. doi: 10.22038/ijbms.2018.25366.6269
Hassanzadeh, Abdolreza, Mandegary, Ali, Sharif, Elham, Rasooli, Rokhsana, Mohammadnejad, Reza, Masoumi, Yaser. Cyclooxygenase inhibitors combined with deuterium-enriched water augment cytotoxicity in A549 lung cancer cell line via activation of apoptosis and MAPK pathways. , 1397; 21(5): 508-516. doi: 10.22038/ijbms.2018.25366.6269

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
مقاله 11، دوره 21، شماره 5، مرداد 2018، صفحه 508-516    اصل مقاله (869.17 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2018.25366.6269
نویسندگان
Abdolreza Hassanzadeh1، 2؛ Ali Mandegary* 3، 4؛ Elham Sharif1، 4؛ Rokhsana Rasooli1، 4؛ Reza Mohammadnejad1، 4؛ Yaser Masoumi5
1Pharmaceutics Research Centre, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
2Department of Medicinal Chemistry, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
3Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
4Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
55 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
چکیده
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.
کلیدواژه‌ها
A549 lung cancer cell؛ Apoptosis؛ Combination therapy؛ Cyclooxygenase inhibitors؛ Deuterium enriched water؛ MAPK pathway
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