Induction of differentiation of human leukemia cells by combinations of COX inhibitors and 1, 25-dihydroxyvitamin D3 involves Raf1 but not Erk 1/2 signaling

Cox-2 inhibitors induce early c-Myc downregulation and lead to expression of differentiation markers in leukemia cells

“…In this context, an enhancement of 1,25D-induced differentiation has been obtained with NSAIDs (indomethacin) and COX-2 inhibitors (DUP-697). 75 In this study, this effect was associated with an enhancement of Raf1 phosphorylation and a decrease of ERK1/2 phosphorylation in HL-60 and U937 cells. Moreover, in another study the abrogation of Cot1 oncogene, associated to an inhibition of its downstream target ERK5, sensitizes AML cell models to 1,25D-induced differentiation.…”

“…Similarly, 1,25-dihydroxyvitamin D 3 (1,25D) displays an ability to induce differentiation in leukemic cells. 75 However, the clinical use of this drug bears the risk of severe side effects, such as hyperkalemia. 76 Thus, efforts are being placed on a combination …”

Enhancement of 1,25-Dihydroxyvitamin D3- and All-transRetinoic Acid-Induced HL-60 Leukemia Cell Differentiation byPanax ginseng

“…ATRA combinations with histone deacetylase inhibitors, 19) gefitinib, 20) and carnosic acid 21) have exerted synergistic effects on HL-60 leukemia cell differentiation. In the same way, capsaicin, 22) ascorbate, 23) and cyclooxygenase inhibitors 24) have enhanced the HL-60 cell differentiation produced by a low level of 1,25-(OH) 2 D 3 . Such analogues of vitamin D 3 as 1,25-(OH) 2 D 3 are used clinically for the treatment of psoriasis.…”

Induction of human leukemia cell differentiation via PKC/MAPK pathways by arsantin, a sesquiterpene lactone from Artemisia santolina

“…Many previous studies have shown some chemical combinations which exerted an additive or synergistic effect on HL-60 cell differentiation. These combinations include plant-derived compounds and ATRA or 1,25-(OH) 2 D 3 (Kim et al 2008), arsenic trioxide and ATRA (Wang and Chen 2008), COX inhibitors and 1,25-(OH) 2 D 3 (Jamshidi et al 2008), histone deacetylase inhibitors and RA (Savickiene et al 2006), and AM-80 and ATRA (Ishida et al 2004). The mechanism by which arsantin induces HL-60 cell differentiation is not clear.…”