Novel target genes responsive to the anti-growth activity of triptolide in endometrial and ovarian cancer cells.
Triptolide (TPL), a bioactive component of the Chinese medicinal herb Tripterygium wilfordii Hook F, induces apoptosis in some lines of human tumor cells. However, the effect of TPL on gynecologic cancer cells has not yet been well-described. We investigated the effects of TPL on cell growth, cell cycle, and apoptosis in endometrial and ovarian cancer cell lines. Furthermore, we examined global changes in gene expression after treatment with TPL. By using a list of 20 differentially expressed genes, Western blot analyses were performed on five endometrial and ovarian cancer cell lines. All cell lines were sensitive to the growth-inhibitory effect of TPL. TPL increased the proportion of cells in the S-phase of the cell cycle and induced apoptosis. cDNA microarray assay demonstrated that the treatment with TPL changed the expression of cell cycle regulators, apoptosis-related factors and cell proliferation markers. Of the gene expression changes induced by TPL treatment, up-regulation of LRAP, CDH4, and SFRP1 and down-regulation of cystatin, TNNT 1, and L1-CAM were confirmed using Western blot analysis in all the cell lines examined. We found a strong anticancer activity of TPL and identified some potential target genes of this drug, raising hopes that TPL may become a useful therapy for endometrial and ovarian cancers.
Li
Haili
H
Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan.
Takai
Noriyuki
N
Yuge
Akitoshi
A
Furukawa
Yuichi
Y
Tsuno
Akitoshi
A
Tsukamoto
Yoshiyuki
Y
Kong
Shigi
S
Moriyama
Masatsugu
M
Narahara
Hisashi
H
D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology*; D029757:Tripterygium / Q000737:chemistry
D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide