1.Dipyrone & 2,5-dimethylcelecoxib suppress Th2-related chemokine production in monocyte.
Shiang JC, Jan RL, Tsai MK, Hsieh CC, Kuo HF, Kuo CH, Yang SN, Huang MY, Chen LC, Hung CH1. Indian J Med Res. 2014 Jul;140(1):109-15.
BACKGROUND & OBJECTIVES: Selective cyclooxygenase-2 (COX-2) inhibitor is a form of thnon steroidal anti-inflammatory drug (NSAID) and is commonly used in autoimmune and rheumatic diseases to control inflammation and alleviate pain. Tumour necrosis factor-alpha (TNF-α) production and an imbalance of T helper 1 (Th1)/Th2 contribute to the pathogenesis of autoimmune and also anti-tumour activity. Dipyrone is a NSAID used to treat pain worldwide. The celecoxib analogue, 2,5-dimethylcelecoxib (DMC), lacks COX-2 inhibitory activity but exhibits anti-tumour properties. However, the effects and the mechanisms of dipyrone and 2,5-dimethylcelecoxib on tumour necrosis factor (TNF)-α and Th1- and Th2-related chemokines in monocytes remain poorly defined. This study was carried out to investigate the effects of dipyrone and 2,5-dimethylcelecoxib on the expression of Th1 (IP-10) and Th2 (I-309 and MDC) and TNF-α in human monocytes and the associated intracellular mechanism.
2.2,5-Dimethyl-celecoxib inhibits cell cycle progression and induces apoptosis in human leukemia cells.
Sobolewski C1, Rhim J1, Legrand N1, Muller F1, Cerella C1, Mack F1, Chateauvieux S1, Kim JG1, Yoon AY1, Kim KW1, Dicato M1, Diederich M2. J Pharmacol Exp Ther. 2015 Nov;355(2):308-28. doi: 10.1124/jpet.115.225011. Epub 2015 Sep 1.
Cyclooxygenase-2 (COX-2) is an essential regulator of cancer promotion and progression. Extensive efforts to target this enzyme have been developed to reduce growth of cancer cells for chemopreventive and therapeutic reasons. In this context, cyclooxygenase-2 inhibitors present interesting antitumor effects. However, inhibition of COX-2 by anti-COX-2 compounds such as celecoxib was recently associated with detrimental cardiovascular side effects limiting their clinical use. As many anticancer effects of celecoxib are COX-2 independent, analogs such as 2,5-dimethyl-celecoxib (DMC), which lacks COX-2-inhibitory activity, represent a promising alternative strategy. In this study, we investigated the effect of this molecule on growth of hematologic cancer cell lines (U937, Jurkat, Hel, Raji, and K562). We found that this molecule is able to reduce the growth and induces apoptosis more efficiently than celecoxib in all the leukemic cell lines tested.