Tumor cell differentiation by butyrate and environmental stress.
The present study shows that stress signaling plays a role in differentiation of K562, PANC1, HT29 and HL60 tumor cells: (1) Butyrate induced differentiation in K562, PANC1, and HT29 cells can be inhibited by SB203580, a specific inhibitor of p38 stress activated protein kinase. (2) Heat shock and hyperosmolarity increase expression of differentiation markers in K562, HT29, HL60 and in K562, PANC1, and HT29 cells, respectively. (3) Conversely, environmental stress induced differentiation in K562, HT29, and PANC1 cells can be inhibited by SB203580 and quercetin, a compound with heat shock pathway 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 pharmacologic target for differentiation therapy of malignant disease.
Witt
O
O
Children's hospital, University of Göttingen, Robert-Koch-Street 40, D-37075 Göttingen, Germany. owitt@gwdg.de
Schulze
S
S
Kanbach
K
K
Roth
C
C
Pekrun
A
A
D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects; D019073:HT29 Cells / Q000166:cytology / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020014:K562 Cells / Q000166:cytology / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D009994:Osmolar Concentration; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases
D002087:Butyrates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D011794:Quercetin; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580