Activation of PPARγ mediates icaritin-induced cell cycle arrest and apoptosis in glioblastoma multiforme
Authors: Weiping Zhu
Yongji Liu
Hongxing Han
Yongbin Zhang
Guoping Jiang
Yuan Liu
Xiaoning Gao
Fang Ju
Ling Shi
Chuanwu Jiang
Peng Li
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AMPK; GBM; Icaritin; PPARγ.
Affiliations: Department of Neurosurgery, The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China. Electronic address: ., Department of Neurosurgery, The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China., Department of Emergency, The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China., Department of Radiology, The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China., Department of Rheumatology and Immunology, The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China., Department of Neurology, Linyi People's Hospital, Linyi, Shandong, China., Department of Oncology, Qingdao Central Hospital, Qingdao, Shandong, China. Electronic address: .

Abstract:  Background: Glioblastoma multiforme (GBM) is the most prevalent primary malignancy of the brain. This study was designed to investigate whether icaritin exerts anti-neoplastic activity against GBM in vitro. Materials and methods: Cell Counting Kit-8 (CCK-8) assay was utilized to examine the viability of GBM cells. The apoptotic cell population was measured by flow cytometry analysis. Cell cycle distribution was detected by flow cytometry as well. Western blot analysis was performed to examine the level of biomarker proteins in GBM cells. Levels of PPARγ mRNA and protein were detected by qPCR and western blot analysis, respectively. To examine the role of PPARγ in the anti-neoplastic activity of icaritin, PPARγ antagonist GW9662 or PPARγ siRNA was used. The activity of PPARγ was determined by DNA binding and luciferase assays. Results: Our findings revealed that icaritin markedly suppresses cell growth in a dose-dependent and time-dependent fashion. The cell population at the G0/G1 phase of the cell cycle was significantly increased following icaritin treatment. Meanwhile, icaritin promoted apoptotic cell death in T98G and U87MG cells. Further investigation showed upregulation of PPARγ played a key role in the anti-neoplastic activities of icaritin. Moreover, our result demonstrated activation of AMPK signaling by icaritin mediated the modulatory effect of icaritin on PPARγ. Conclusion: Our results suggest the PPARγ may mediate anti-neoplastic activities against GBM. 

Retracted: No

PubPeer comments:
 Fig 5A.  PPARu03b3 antagonist (GW9662) attenuates the pro-apoptotic activity of icaritin in T98G and U87MG cells. Glioma cells were pretreated with GW9662 for 6 h before incubated with icaritin for 48 h before assays were performed. A. GW9662 significantly attenuates the prop-apoptotic effect of icaritin. I have many concerns, such as the similarity of the Attentuated-U87MG results to the T98G control, apart from additional cells in the upper right quadrant. And the similarity of Icaritin-U87MG results to the Attenuated-T98G results, apart from a clump of points in the lower right quadrant and what appears to be an phalanx of of Space Invaders in the upper right. ![file] Note also that the U87MG Control has appeared many many times elsewhere in this oeuvre of papers, identified as different cell-lines. ![file] Or Fig 1D of [Zou et al (2018)] : ![file] ,