Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo .

Autor:	Du R; Chifeng Municipal Hospital, Chifeng, China.; Clinic for Neurosurgery, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany., Sanin AY; Molecular and Experimental Surgery, Clinic for General-, Visceral -, Vascular- and Transplantation Surgery, Medical Faculty and University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany., Shi W; Molecular and Experimental Surgery, Clinic for General-, Visceral -, Vascular- and Transplantation Surgery, Medical Faculty and University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany., Huang B; FORM, Frankfurt Oral Regenerative Medicine, Clinic for Maxillofacial and Plastic Surgery, Goethe University, Frankfurt Am Main, Germany.; Department of Cardiothoracic Surgery, First Affiliated Hospital of Shihezi University, Shihezi, China., Nickel AC; Clinic for Neurosurgery, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany., Vargas-Toscano A; Clinic for Neurosurgery, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany., Huo S; Chifeng Cancer Hospital, Chifeng, China., Nickl-Jockschat T; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany., Dumitru CA; Clinic for Neurosurgery, Medical Faculty and University Hospital Magdeburg, Otto von Guericke University, Magdeburg, Germany., Hu W; Chifeng Municipal Hospital, Chifeng, China., Duan S; Chifeng Municipal Hospital, Chifeng, China., Sandalcioglu IE; Clinic for Neurosurgery, Medical Faculty and University Hospital Magdeburg, Otto von Guericke University, Magdeburg, Germany., Croner RS; Molecular and Experimental Surgery, Clinic for General-, Visceral -, Vascular- and Transplantation Surgery, Medical Faculty and University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany., Alcaniz J; Experimental Pharmacology and Oncology Berlin-Buch GmbH, Berlin, Germany., Walther W; Experimental Pharmacology and Oncology Berlin-Buch GmbH, Berlin, Germany., Berndt C; Clinic for Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany., Kahlert UD; Molecular and Experimental Surgery, Clinic for General-, Visceral -, Vascular- and Transplantation Surgery, Medical Faculty and University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 Sep 25; Vol. 15, pp. 1468920. Date of Electronic Publication: 2024 Sep 25 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1468920
Abstrakt:	Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further. Competing Interests: Authors JA and WW were employed by Experimental Pharmacology and Oncology Berlin-Buch GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Du, Sanin, Shi, Huang, Nickel, Vargas-Toscano, Huo, Nickl-Jockschat, Dumitru, Hu, Duan, Sandalcioglu, Croner, Alcaniz, Walther, Berndt and Kahlert.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu