The experimental and clinical study on the effect of curcumin on cell cycle proteins and regulating proteins of apoptosis in acute myelogenous leukemia.
- Author:
Yan, CHEN
;
Yudan, WU
;
Jing, HE
;
Wenjuan, CHEN
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents, Phytogenic/pharmacology;
Apoptosis/*drug effects;
Cell Cycle Proteins/*metabolism;
Curcumin/*pharmacology;
Genes, bcl-2/genetics;
HL-60 Cells;
Leukemia, Myelocytic, Acute/pathology;
Neoplasm Proteins/biosynthesis;
Neoplasm Proteins/genetics;
Proto-Oncogene Proteins/biosynthesis;
Proto-Oncogene Proteins/genetics;
Proto-Oncogene Proteins c-bcl-2/*metabolism;
Tumor Cells, Cultured;
bcl-2-Associated X Protein
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2002;22(4):295-8
- CountryChina
- Language:English
-
Abstract:
To investigate whether the Bcl-2 gene family is involved in modulating mechanism of apoptosis and change of cell cycle protein induced by curcumin in acute myeloid leukemia HL-60 cell line and primary acute myelogenous leukemic cells, the Bcl-2 family member Mcl-1, Bax and Bak and cell cycle proteins including P27kipl, P21wafl, cyclin D3 and pRbp- were selected and their expression detected by SABC immuno-histochemical stain method. The attitude of sub-G1 peak in DNA histogram was determined by FCM. The TUNEL positive cell percentage was identified by terminal deoxynucleotidyl transferase (TdT)-mediated Biotin dUNP end labeling technique. It was found that when HL-60 cells were treated with 25 mumol/L curcumin for 24 h, the expression level of Mcl-1 was down-regulated, but that of Bax and Bak up-regulated time-dependently. There was significant difference in the expression level of Mcl-1, Bax and Bak between the curcumin-treated groups and control group (P < 0.05-0.01). At the same time, curcumin had no effect on progress of cell cycle in primaty acute myelogenous leukemia at newly diagnosis, but could increase the peak of Sub-G1 (P < 0.05), and down-regulate the expression of Mcl-1 and up-regulate the expression of Bax and Bak with the difference being statistically significant. The expression of P27kipl, P21wafl and pRbp- were elevated and that of cyclin D3 decreased in the presence of curcumin. These findings suggested that the Bcl-2 gene family indeed participated in the regulatory process of apoptosis induced by curcumin in HL-60 cells and AML cells. Curcumin can induce apoptosis of primary acute myelogenous leukemic cells and disturb cell cycle progression of HL-60 cells. The mechanism appeared to be mediated by perturbing G0/G1 phases checkpoints which associated with up-regulation of P27kipl, P21wafl and pRbp- expression, and down-regulation of cyclin D3.
