Tumor cell differentiation by butyrate and environmental stress

The present study shows that stress signaling plays a role in differentiati on of K562. PANC1, HT29 and HL60 tumor cells: (1) Butyrate induced differen tiation in K562, PANC1 and HT29 cells can be inhibited by SB203580. a speci fic inhibitor of p38 stress activated protein kinase. (2) Heat shock and hy perosmolarity increase expression of differentiation markers in K562. HT29, HL60 and in K562, PANC1, and HT29 cells, respectively. (3) Conversely. env ironmental stress induced differentiation in K562, HT29. and PANC1 cells ca n be inhibited by SB203580 and quercetin, a compound with heat shock pathwa y inhibiting activity. (4) Butyrate and environmental stress enhance either additively or synergistically differentiation of K562, HT29. PANC1 or HL60 cells, respectively. Stress signaling pathways might be an interesting pha rmacologic target for differentiation therapy of malignant disease. (C) 200 1 Elsevier Science Ireland Ltd. All rights reserved.