[Effect of deguelin on proliferation and apoptosis of lymphoma Daudi cells and its mechanism].
OBJECTIVE
To investigate the anticancer effects and molecular mechanism of deguelin on human Burkitt's lymphoma Daudi cells in vitro and compare the cytotoxicity of deguelin on Daudi cells and human peripheral blood monocular cells (HPBMC).


METHODS
The effects of deguelin on the growth of Daudi cells were studied by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5 diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was assessed through Hoechst 33258 staining and annexin V/PI double-labeled cytometry. The effect of deguelin on the cell cycle of Daudi cells was studied by propidium iodide method. The expressions of cyclin D1 and pRb were checked by Western blot.


RESULTS
The proliferation of Daudi cells was decreased in deguelin-treated group with a 24 h IC50 value of 51. 55 nmol/L. Deguelin induced Daudi cells apoptosis in a time- and dose-dependent manner. Daudi cells treated with deguelin showed an increase of G0/G1 phase and decrease of S phase. The Daudi cells treated with 0, 5, 10, 20, 40 nmol/L deguelin for 24 h, showed an increased Go/G, phase from 37.34% to 56.56% , whereas decreased S phase from 37.72% to 21.36%, respectively. PBMC was less sensitive to the cytotoxic effect of deguelin than Daudi cells. The expression of cyclin D1 and pRb protein were decreased in Daudi cells treated with deguelin.


CONCLUSIONS
Deguelin can inhibit the proliferation of Daudi cells by regulating the cell cycle that arrest cells at G0/G1 phase and inducing apoptosis. Moreover, deguelin demonstrats low toxicity in PBMC but selectively induces apoptosis of Daudi cells. The antitumor effects of deguelin may be related to down-regulation of the expression of cyclin D1 and pRb protein.
Liu
Hong-li
HL
Institute of Hematology, Union Hospital, Tongdi Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. liuhl60@hotmail.com
Chen
Yan
Y
Cui
Guo-hui
GH
Wu
Qiu-ling
QL
Chen
Wei-hua
WH
He
Jing
J
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D012402:Rotenone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D016160:Retinoblastoma Protein; D012402:Rotenone; D019938:Cyclin D1; C107676:deguelin