Induction of apoptosis in K562 human leukemia cells by 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone.
2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), isolated from the buds of Cleistocalyx operculatus, was investigated in its cytotoxicity and anti-proliferation on K562 cell line. Our results revealed that the IC50 was equal to 14.2+/-0.45 microM and the EC50 was 3.3+/-0.14 microM. Staining with Hoechst 33258 showed fragmentation and condensation of chromatin in the cells treated with 8 microM DMC for 48 h. Flow cytometric analysis was performed to determine hypodiploid cells. The results of flow cytometry assay indicated that the percentage of hypodiploid K562 cells was 76.15+/-3.22% after 48 h treatment with 16.0 microM DMC. The treatment resulted in the appearance of a hypodiploid peak (A0 region), probably due to the presence of apoptosing cells and/or apoptotic bodies with DNA content less than 2n. Western blot results illustrated that in the same dosage and incubation time, DMC could down-regulate the level of Bcl-2 protein and did not influence the expression of Bax protein. The resulting net effect could thus lead to a lower ratio of Bcl-2/Bax, which might be responsible for the DMC-induced apoptosis in K562 cells.
State Key Laboratory of Bioreactor Engineering, Institute of Biochemistry, East China University of Science and Technology, Shanghai 200237, PR China.
Chun-Lin
CL
Ye
Feng
F
Qian
Dong-Zhi
DZ
Wei
Yan-Hua
YH
Lu
Jian-Wen
JW
Liu
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047188:Chalcones; D003114:Colony-Forming Units Assay; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000473:pathology; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects; D051028:bcl-2-Associated X Protein
C501649:2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; C494826:BAX protein, human; D047188:Chalcones; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002599:Chalcone