Natural jasmonates of different structures suppress the growth of human neuroblastoma cell line SH-SY5Y and its mechanisms.
OBJECTIVE
Recent evidence has indicated that members of natural jasmonates, a family of plant stress hormones, exhibit anticancer activity. The current study was undertaken to investigate the effects of jasmonates on the in vitro growth of human neuroblastomas, one of the most common solid tumors in children.


METHODS
Cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide colorimetry and colony formation assay. Apoptosis was detected by Hoechst 33258 staining and flow cytometry. Western blotting was applied to assay gene expression.


RESULTS
The administration of natural jasmonates, methyl jasmonate, cis-jasmone, and jasmonic acid to cultured neuroblastoma cell line SH-SY5Y, resulted in a decrease of cell proliferation in a doseand time-dependent manner. However, the in vitro growth of cultured human embryonic kidney (HEK) cell line HEK 293 was not affected by jasmonates. The cell cycles of jasmonate-treated SH-SY5Y cells were arrested at the G2/M phase. The incubation of SH-SY5Y cells with jasmonates resulted in characteristic changes of apoptosis. The anticancer activities of natural jasmonates on SH-SY5Y cells are as follows: methyl jasmonate>cis-jasmone>jasmonic acid. In addition, the expressions of proliferating cell nuclear antigen and N-myc were downregulated by methyl jasmonate. Moreover, methyl jasmonate decreased the expression of the Xlinked inhibitor of apoptosis protein and survivin, critical members of inhibitors of the apoptosis protein family, in SH-SY5Y cells.


CONCLUSIONS
Jasmonates suppress the growth of human neuroblastoma cell line SH-SY5Y via inhibiting cell proliferation and inducing apoptosis, which lays the groundwork for further investigation into the anticancer activities and its mechanisms of natural jasmonates on human neuroblastomas.
Department of Surgery, Huazhong University of Science and Technology, Wuhan 430022, China. qs_tong@hotmail.com
Qiang-song
QS
Tong
Guo-song
GS
Jiang
Li-duan
LD
Zheng
Shao-tao
ST
Tang
Jia-bin
JB
Cai
Yuan
Y
Liu
Fu-qing
FQ
Zeng
Ji-hua
JH
Dong
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D031660:Jasminum / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D054883:Oxylipins / Q000737:chemistry / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D000077022:Survivin; D014410:Tumor Stem Cell Assay; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis / Q000235:genetics
D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D003517:Cyclopentanes; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D054883:Oxylipins; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human