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.

Cell Cycle
Farnaz JamshidiGeorge P Studzinski

Abstract

Differentiation therapy of cancer is being explored as a potential modality for treatment of myeloid leukemia, and derivatives of vitamin D are gaining prominence as agents for this form of therapy. Cyclooxygenase (COX) inhibitors have been reported to enhance 1,25-dihydroxyvitamin D(3) (1,25D)-induced monocytic differentiation of promyeloblastic HL60 cells, but the mechanisms of this effect are not fully elucidated, and whether this potentiation can occur in other types of myeloid leukemia is not known. We found that combination treatment with 1,25D and non-specific COX inhibitors acetyl salicylic acid (ASA) or indomethacin can robustly potentiate differentiation of other types of human leukemia cells, i.e., U937, THP-1, and that ASA +/- 1,25D is effective in primary AML cultures. Increased cell differentiation is paralleled by arrest of the cells in the G(1) phase of the cell cycle, and by increased phosphorylation of Raf1 and p90RSK1 proteins. However, there is no evidence that this increase in phosphorylation of Raf1 is transmitted through the ERK module of the MAPK signaling cascade. Transfection of small interfering (si) RNA to Raf1 decreased differentiation of U937 cells induced by a combination of ASA or indomethacin wi...Continue Reading

Citations

Aug 5, 2009·Critical Reviews in Clinical Laboratory Sciences·Elzbieta Gocek, George P Studzinski
Oct 20, 2015·Critical Reviews in Clinical Laboratory Sciences·Surojit SarkarVandana Kalia
Nov 22, 2011·Expert Opinion on Therapeutic Patents·Deniz EkinciÖmer İrfan Küfrevioğlu
Aug 5, 2015·Journal of Clinical Medicine·Elzbieta Gocek, George P Studzinski
Feb 20, 2015·Journal of Cellular Biochemistry·George P StudzinskiMichael Danilenko
Feb 12, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Dong-Oh MoonSung Gyu Yun
Jul 30, 2014·Frontiers in Physiology·Thea K WöbkeDieter Steinhilber
Jan 1, 2011·Cancers·Elzbieta Gocek, Ewa Marcinkowska

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