HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells.

Abstract
The acute promyelocytic leukemia (APL) has been treated with all-trans retinoic acid (RA) for decades. While RA has largely been ineffective in non-APL AML subtypes, co-treatments combining RA and other agents are currently in clinical trials. Using the RA-responsive non-APL AML cell line HL-60, we tested the efficacy of the Src family kinase (SFK) inhibitor bosutinib on RA-induced differentiation. HL-60 has been recently shown to bear fidelity to a subtype of AML that respond to RA. We found that co-treatment with RA and bosutinib enhanced differentiation evidenced by increased CD11b expression, G1/G0 cell cycle arrest, and respiratory burst. Expression of the SFK members Fgr and Lyn was enhanced, while SFK activation was inhibited. Phosphorylation of several sites of c-Raf was increased and expression of AhR and p85 PI3K was enhanced. Expression of c-Cbl and mTOR was decreased. Our study suggests that SFK inhibition enhances RA-induced differentiation and may have therapeutic value in non-APL AML.
AuthorsRobert J MacDonald, Rodica P Bunaciu, Victoria Ip, David Dai, David Tran, Jeffrey D Varner, Andrew Yen
JournalLeukemia & lymphoma (Leuk Lymphoma) Vol. 59 Issue 12 Pg. 2941-2951 (12 2018) ISSN: 1029-2403 [Electronic] United States
PMID29569971 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Aniline Compounds
  • Nitriles
  • Quinolines
  • bosutinib
  • Tretinoin
  • src-Family Kinases
Topics
  • Aniline Compounds (pharmacology, therapeutic use)
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
  • Cell Differentiation (drug effects)
  • Drug Resistance, Neoplasm (drug effects)
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid, Acute (drug therapy, pathology)
  • Nitriles (pharmacology, therapeutic use)
  • Quinolines (pharmacology, therapeutic use)
  • Signal Transduction (drug effects)
  • Tretinoin (pharmacology)
  • src-Family Kinases (antagonists & inhibitors, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: