Fructus ligustri lucidi extracts induce human glioma cell death through regulation of Akt/mTOR pathway in vitro and reduce glioma tumor growth in U87MG xenograft mouse model.
The present study was undertaken to examine the effect of Fructus ligustri lucidi (FLL) extracts on glioma cell growth and to determine the underlying mechanism by which FLL extracts exert anticancer properties in human U87MG glioma cells. The FLL extracts resulted in cell death in a dose- and time-dependent manner. Western blot analysis showed that treatment with FLL extracts caused down-regulation of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Overexpression of Akt prevented the cell death induced by the FLL extracts. The FLL extracts caused a decrease in the expression of mammalian target of rapamycin (mTOR) and the FLL extract-induced cell death was increased by the mTOR inhibitor rapamycin. The FLL extracts decreased the expression of survivin. Oral administration of FLL extracts in subcutaneous U87MG xenograft models reduced the glioma tumor volume. These findings indicate that the FLL extracts resulted in glioma cell death through regulation of the Akt/mTOR/survivin pathway in vitro and inhibited glioma tumor growth in vivo. These data suggest that the FLL extracts may serve as a potential therapeutic agent for malignant human gliomas.
Jeong
Ji Cheon
JC
Department of Oriental Medicine, Dongguk University, Kyung Ju, 780-714, Korea.
Kim
Jin Won
JW
Kwon
Chae Hwa
CH
Kim
Thae Hyun
TH
Kim
Yong Keun
YK
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D031659:Ligustrum / Q000737:chemistry*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077022:Survivin; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D051034:Inhibitor of Apoptosis Proteins; D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D000077022:Survivin; D058570:TOR Serine-Threonine Kinases; C107489:BIRC5 protein, human