Effects Of Curcumin And Its Derivative C086on Chronic Myeloid Leukemia In Vitro And Its Possible Mechanism

Objective: To study the effects of curcumin and its derivatives C086on apoptosisinduction in imatinib-sensitive or resistant leukemia cells, and clarify the mechanismof mitochondira pathway activation.Methods:（1） MTT assay was used for cell proliferation determination in vitro aftereither Cur or C086treatment.（2） Detect the apoptotic induction by either C086orCur in leukemia cells by AnnexinV-FITC/PI double staining examined by flowcytometry.（3）Observe the change of mitochondrial membrane potential by JC^-1staining after either C086or Cur treatment in leukemia cells.（4） Analyze cell cyclealteration.induced by either C086or Cur by PI staining examined by flow cytometry.（5） Determine cell division inhibition after either C086or Cur treatment via CFSEstaining examined by flow cytometry.（6） Test the effect of either C086or Cur onCD34+progenitor/stem cells from bone marrow of CML patients by the trypan bluestaining.（7） Test the effect of either C086or Cur on colony formation of CD34+progenitor/stem cells..（8）Analyse the effect of either C086or Cur on self-renewfunction of leukemia stem cell by counting long term culture-initiating cells（LTC-IC）.（9） Western blot was used to detect the alteration of protein amount inCML cells after either Cur or C086treatment.Results:（1） C086inhibited the proliferation of K562and K562/G01cells indose-dependent and concentration-dependent manner.（2） C086increasedmitochondrial membrane potential dissipation degree in leukemia cells significantly.（4） C086or Cur blocked leukemia cell in the G2/M phase of the cell cycledramatically.（5） C086significantly suppressed the division of leukemia cells testedby CFSE staining.（6） Both C086and Cur could kill CD34+progenitor/stem cellsfrom CML patients.（7） Both C086and Cur were able to inhibit colony formingability of CD34+progenitor/stem cell from CML patients’ bone marrow.（8） Both C086and Cur have capability of inhibiting self-renew function ofleukemia stem cellsby long-term culture initiating cells assay.（9） Both C086and Cur have effects ofapoptosis induction of leukemia cells via activating caspase-9/caspase-3mitochondrial pathway.Conclusion: Both curcumin and its derivative C086have the potential to inducethe apoptosis of CML cells via activating caspase-9/caspase-3mitochondrial pathwayinhibit proliferation; moreover arrest self-renew function of LSC from CML patients.