Artesunate inhibits cell proliferation and decreases growth hormone synthesis and secretion in GH3 cells.
To determine the effect of artesunate (ART) on the rat pituitary adenoma GH3 cell line to evaluate its potential as a novel agent in growth hormone (GH) adenoma and to investigate its underlying mechanisms of action. The MTT assay was used to assess cell proliferation. DAPI staining was used to visualise apoptotic changes in the nucleus. We also analyzed cell apoptosis and cell cycle stage by flow cytometry, semi-quantitative RT-PCR analysis for the expression of GH mRNA and apoptosis-induced factor (AIF) mRNA, analysis of GH protein by western blot, ELISA detection of secreted GH, and the caspase inhibition assay. We found that ART inhibited the proliferation of GH3 cells in a dose- and time-dependent manner, with an IC50 of 9.53 ± 4.12 μM. The IC50s of ART against of two normal cell lines (mouse embryonic fibroblasts, and rat bone mesenchymal cells) were much higher than the IC50 recorded for the GH3 cells. ART induced apoptosis and blocked GH3 at G2/M arrest. The pan caspase inhibitor V-ZAD-FMK partly attenuated the inhibitory effect of ART. ART increased the expression of AIF mRNA and reduced GH mRNA levels, GH synthesis and the secretion of GH level in GH3 cells. ART can inhibit proliferation and induce apoptosis in GH3 cells by caspase-dependent pathways. Additionally, ART can inhibit GH synthesis and secretion. Thus, we propose ART as a probably anti-tumour candidate drug in the treatment of GH adenoma.
Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Zhi-Gang
ZG
Mao
Jing
J
Zhou
Hui
H
Wang
Dong-Sheng
DS
He
Wei-Wei
WW
Xiao
Gui-Zhi
GZ
Liao
Lu-Bin
LB
Qiu
Yong-Hong
YH
Zhu
Hai-Jun
HJ
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D037621:Artemisinins; D012333:RNA, Messenger; D000077332:Artesunate; D013006:Growth Hormone; D020169:Caspases