Regulating expressions of cyclin D1, pRb, and anti-cancer effects of deguelin on human Burkitt's lymphoma Daudi cells in vitro.
OBJECTIVE
To investigate anticancer effects and molecular mechanism of deguelin on human Burkittos lymphoma Daudi cells in vitro and compare the cytotoxicities of deguelin on Daudi cells and human peripheral blood monocular cells (PBMC).


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 were detected through Hoechst 33258 staining and Annexin V/PI double-labeled cytometry. The effect of deguelin on the cell cycle of Daudi cells were studied by a propidium iodide method. The expressions of cyclin D1 and pRb were checked by Western blot.


RESULTS
The proliferation of Daudi cells were decreased in deguelin-treated group with a 24-h IC50 value of 51.55 nmol/L. Deguelin induced Daudi cells apoptosis was in a time- and dose-dependent manner. G0/G1 phase increased and S phase decreased in Daudi cells treated with deguelin. With deguelin 0, 5, 10, 20, and 40 nmol/L treatment for 24 h, G0/G1 phase increased from 37.34% to 56.56%, whereas S phase decreased from 37.72% to 21.36%. PBMC was less sensitive to the cytotoxic effect of deguelin than Daudi cells. The expression of cyclin D1 and pRb protein were decreased sharply in Daudi cells treated with deguelin.


CONCLUSIONS
Deguelin is able to inhibit the proliferation of Daudi cells by regulating the cell cycle that arrested cells at G0/G1 phase and inducing the cell apoptosis. Moreover, deguelin selectively induced apoptosis of Daudi cells with low toxicity in PBMC. The antitumor effects of deguelin were related to down-regulating the expression of cyclin D1 and pRb protein.
Liu
Hong-Li
HL
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. liuhl60@tom.com
Chen
Yan
Y
Cui
Guo-Hui
GH
Wu
Qiu-Ling
QL
He
Jing
J
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis; 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; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; 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