[Effect of betulinic acid on proliferation and apoptosis in Jurkat cells and its mechanism].
OBJECTIVE
To investigate the anticancer effects of betulinic acid (BA) on Jurkat cells in vitro and its molecular mechanism.


METHODS
The effects of betulinic acid on the growth of Jurkat cells were studied by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was assessed by Hoechst33258 staining and annexin-V/PI double-labeled cytometry. The effect of betulinic acid on the cell cycle of Jurkat cells was studied by propidium iodide staining. RT-PCR and Western blot were used to analyze the changes of cyclin D3, bcl-xl mRNA and protein levels in Jurkat cells after treatment with betulinic acid.


RESULTS
The proliferation of Jurkat cells was decreased in betulinic acid-treated group at a 24 h IC50 value of 70.0 micromol/L. The effect of betulinic acid to induce apoptosis in Jurkat cells was in a time- and dose-dependent manner. Jurkat cells treated with betulinic acid showed an increase of G0/G1 phase and decrease of S phase. The Jurkat cells treated with 0, 20, 60, 100 micromol/L betulinic acid for 24 h, showed an increased G0/G1 phase from 31.0% to 58.8%, whereas decreased S phase from 61.5% to 35.8%, respectively. PBMC was less sensitive to the cytotoxic effect of betulinic acid than Jurkat cells. The expression of cyclin D3, bcl-xl mRNA and protein were decreased sharply in Jurkat cells treated with betulinic acid.


CONCLUSIONS
Betulinic acid can inhibit the proliferation of Jurkat cells by regulating the cell cycle that arrests cells at G0/G1 phase and induces apoptosis in Jurkat cells. The antitumor effects of betulinic acid may be related to down-regulation of the expression of cyclin D3 and bcl-xl.
Chen
Zi
Z
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Wu
Qiu-ling
QL
Chen
Yan
Y
He
Jing
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D029662:Betula / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D053978:Pentacyclic Triterpenes; D024301:Plant Bark / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; D056743:Cyclin D3; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger; D014315:Triterpenes; D051020:bcl-X Protein; D000094062:Betulinic Acid