Crotonoside

Crotonoside is isolated from Chinese medicinal herb, Croton. Crotonoside inhibits FLT3 and HDAC3/6, exhibits selective inhibition in acute myeloid leukemia (AML) cells. Crotonoside could be a promising new lead compound for the treatment of AML[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FLT3

Signaling Pathways >> Cell Cycle/DNA Damage >> HDAC

Signaling Pathways >> Epigenetics >> HDAC

FLT3

HDAC3

HDAC6

Crotonoside (0-200 μM;) selectively inhibits the viability of AML cell line MV4-11, MOLM-13 (with FLT3-ITD mutant) and KG-1 (without FLT3-ITD mutant) in a dose-dependent manner with an IC50 of 11.6 μM, 12.7 μM and 17.2 μM, respectively[1]. Crotonoside (0-100μM; 7 hours) inhibits the phosphorylation of FLT3 Erk1/2, Akt/mTOR and STAT5 is strongly inhibited by crotonoside at higher concentration of 12.5 μM in a concentration-dependent manner[1]. Crotonoside (0-100 μM; 12 hours) exhibits a dose-dependent increase in the percentage of G0/G1 phase and a dose-dependent decrease in the percentage of G2/M and S phases cells[1]. Crotonoside (0-100 μM; 24 hours) leads to concentration-dependent changes in the number of apoptotic MV4-11 cells, results in a dose-dependent decrease in the level of pro-caspase-3 and a dose-dependent increase in the level of the cleaved caspase-3 fragments[1]. Cell Viability Assay[1] Cell Line: AML cell line MV4-11, MOLM-13 and KG-1 cells Concentration: 0-200 μM Incubation Time: 72 hours Result: Inhibited AML cells growth than other cell lines tested. Western Blot Analysis[1] Cell Line: MV4-11 cells Concentration: 0 μM, 12.5 μM, 25 μM, 50 μM Incubation Time: 7 hours Result: Inhibited AML cells growth than other cell lines tested. Cell Cycle Analysis[1] Cell Line: MV4-11 cells Concentration: 0 μM, 12.5 μM, 25 μM, 50 μM Incubation Time: 12 hours Result: Induced cell cycle arrest in G0/G1. Apoptosis Analysis[1] Cell Line: MV4-11 cells Concentration: 0 μM, 12.5 μM, 25 μM, 50 μM Incubation Time: 24 hours Result: Induced MV4-11 cell apoptosis.

Crotonoside(intraperitoneal and intravenous injection; 70 mg/kg, 35 mg/kg; once daily) induces a significant antitumor activity and inhibited xenograft tumor progress as compared to treatment with vehicle[1]. Animal Model: NOD-SCID mice with MV4-11 cells[1] Dosage: 70 mg/kg, 35 mg/kg Administration: Intraperitoneal and intravenous injection; 70 mg/kg, 35 mg/kg; once daily Result: Produced significant AML tumor inhibition rates of 93.5% at 70 mg/kg.

[1]. Li YZ,et al. Crotonoside exhibits selective post-inhibition effect in AML cells via inhibition of FLT3 and HDAC3/6. Oncotarget. 2017 Sep 8;8(61):103087-103099.