Methyl jasmonate downregulates expression of proliferating cell nuclear antigen and induces apoptosis in human neuroblastoma cell lines.
Recent evidence indicates that methyl jasmonate, a plant stress hormone, exhibits anticancer activity on human cancer cells. Whether methyl jasmonate could inhibit the growth of human neuroblastoma cells still, however, remains largely unknown. In this study, administration of methyl jasmonate to cultured neuroblastoma cell lines, SK-N-SH and BE(2)-C, resulted in a decrease of cell viability in a dose-dependent and time-dependent manner as demonstrated by MTT colorimetry and colony formation assay. The results from RT-PCR indicated that the expression of proliferating cell nuclear antigen, but not of cyclin D1, was downregulated by methyl jasmonate. Accordingly, the cell cycle of methyl jasmonate-treated neuroblastoma cells was arrested at the G0/G1 phase. Moreover, incubation of SK-N-SH and BE(2)-C cells with methyl jasmonate resulted in characteristic changes of apoptosis, as demonstrated by acridine orange-ethidium bromide (AO/EB) staining, Hoechst 33258 staining and flow cytometry. Moreover, methyl jasmonate decreased the expression of the X-linked inhibitor of apoptosis protein and survivin, critical members of the inhibitors of apoptosis protein family, in neuroblastoma cells. These findings indicate that methyl jasmonate suppresses the growth of cultured human neuroblastoma cells associated with downregulation of proliferating cell nuclear antigen, and induces apoptosis accompanied by downregulation of the X-linked inhibitor of apoptosis protein and survivin, which lays the groundwork for further investigation into the mechanisms of methyl jasmonate-mediated anticancer activities.
Tong
Qiang-Song
QS
Department of Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. qs_tong@hotmail.com
Jiang
Guo-Song
GS
Zheng
Li-Duan
LD
Tang
Shao-Tao
ST
Cai
Jia-Bin
JB
Liu
Yuan
Y
Zeng
Fu-Qing
FQ
Dong
Ji-Hua
JH
D000085:Acetates / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D003517:Cyclopentanes / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D054883:Oxylipins / Q000494:pharmacology*; D010937:Plant Growth Regulators / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors
D000085:Acetates; C107489:BIRC5 protein, human; D003517:Cyclopentanes; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D054883:Oxylipins; D010937:Plant Growth Regulators; D018809:Proliferating Cell Nuclear Antigen; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D019938:Cyclin D1; C072239:methyl jasmonate