Weiyu Zhang1,2, Qiu Du3, Piaopiao Bian4, Zheng Xiao5, Xin Wang6, Yajuan Feng5, Hou Feng5, Ziyan Zhu5, Nailin Gao5, Diming Zhu5, Xiang Fan1,2, Yonghong Zhu5. 1. Department of Neurosurgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. 2. Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. 3. Department of Neurosurgery, The Affiliated Hospital of Yangzhou University, Yangzhou, China. 4. Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. 5. Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 6. Department of Histology and Embryology, Guangdong Pharmaceutical University, Guangzhou, China.
Abstract
BACKGROUND: Prolactinoma is the most common hormone-secreting pituitary adenoma. Dopamine receptor agonists (DAs) are effective in reducing prolactin levels and tumor mass, but some prolactinoma patients are resistant to DAs. Treating patients with DA-resistant prolactinoma is challenging. In this study, we examined the anti-prolactinoma effect of artesunate (ART), a potential new treatment option for prolactinoma, and its mechanism of action. METHODS: Cell Counting Kit-8 (CCK8) and flow cytometry were used to detect the effect of ART on the proliferation, cycle, and apoptosis of rat pituitary adenoma cell line MMQ. The subcellular localization of ART was observed using confocal fluorescence microscopy. The JC-1 mitochondrial membrane potential (MMP) detection and Seahorse assays were used to detect the effect of ART on mitochondrial function. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to detect the effect of ART on the expression of prolactin (PRL) and apoptosis-related proteins. A mouse xenograft model of prolactinoma was used to detect the inhibitory effect of ART on MMQ in vivo. RESULTS: ART specifically inhibited MMQ proliferation and PRL synthesis, induced G0/G1 phase arrest and apoptosis in vitro. ART accumulated in the mitochondria of MMQ cells, inhibiting mitochondrial respiratory function and mediating apoptosis through the mitochondrial pathway. ART also inhibited proliferation and activated the apoptosis of MMQ cells in vivo. CONCLUSIONS: ART has a strong inhibitory effect on prolactinoma both in vitro and in vivo, and its effects rely on high MMP to inhibit mitochondrial metabolism and induce apoptosis. Our results provide evidence for ART as a candidate drug for the treatment of prolactinoma. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Prolactinoma is the most common hormone-secreting pituitary adenoma. Dopamine receptor agonists (DAs) are effective in reducing prolactin levels and tumor mass, but some prolactinoma patients are resistant to DAs. Treating patients with DA-resistant prolactinoma is challenging. In this study, we examined the anti-prolactinoma effect of artesunate (ART), a potential new treatment option for prolactinoma, and its mechanism of action. METHODS: Cell Counting Kit-8 (CCK8) and flow cytometry were used to detect the effect of ART on the proliferation, cycle, and apoptosis of rat pituitary adenoma cell line MMQ. The subcellular localization of ART was observed using confocal fluorescence microscopy. The JC-1 mitochondrial membrane potential (MMP) detection and Seahorse assays were used to detect the effect of ART on mitochondrial function. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to detect the effect of ART on the expression of prolactin (PRL) and apoptosis-related proteins. A mouse xenograft model of prolactinoma was used to detect the inhibitory effect of ART on MMQ in vivo. RESULTS: ART specifically inhibited MMQ proliferation and PRL synthesis, induced G0/G1 phase arrest and apoptosis in vitro. ART accumulated in the mitochondria of MMQ cells, inhibiting mitochondrial respiratory function and mediating apoptosis through the mitochondrial pathway. ART also inhibited proliferation and activated the apoptosis of MMQ cells in vivo. CONCLUSIONS: ART has a strong inhibitory effect on prolactinoma both in vitro and in vivo, and its effects rely on high MMP to inhibit mitochondrial metabolism and induce apoptosis. Our results provide evidence for ART as a candidate drug for the treatment of prolactinoma. 2020 Annals of Translational Medicine. All rights reserved.
Authors: Jessie Yanxiang Guo; Hsin-Yi Chen; Robin Mathew; Jing Fan; Anne M Strohecker; Gizem Karsli-Uzunbas; Jurre J Kamphorst; Guanghua Chen; Johanna M S Lemons; Vassiliki Karantza; Hilary A Coller; Robert S Dipaola; Celine Gelinas; Joshua D Rabinowitz; Eileen White Journal: Genes Dev Date: 2011-02-11 Impact factor: 11.361
Authors: Shereen Ezzat; Sylvia L Asa; William T Couldwell; Charles E Barr; William E Dodge; Mary Lee Vance; Ian E McCutcheon Journal: Cancer Date: 2004-08-01 Impact factor: 6.860