Inhibition of TRPM7 with carvacrol suppresses glioblastoma functions in vivo. (21st March 2022)

• Record Type: Journal Article
• Authors: Alanazi, Rahmah; Nakatogawa, Hirokazu; Wang, Haitao; Ji, Delphine; Luo, Zhengwei; Golbourn, Brian; Feng, Zhong‐Ping; Rutka, James T.; Sun, Hong‐Shuo
• Is Part Of: European journal of neuroscience. Volume 55:Number 6(2022)
• Page Start: 1483
• Page End: 1491
• Publication Date: 2022-03-21
• Subjects: carvacrol -- drug target -- glioblastoma -- in vivo -- ion channels -- TRPM7; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15647
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Glioblastoma (GBM) is the most prevalent and aggressive type of primary human brain tumours originating in the central nervous system. Despite the fact that current treatments involve surgery, chemotherapy (Temozolomide), and radiation therapy, the prognosis for patients diagnosed with GBM remains extremely poor. The standard treatment is not only unable to completely eradicate the tumour cells, but also tumour recurrence after surgical resection presents a major challenge. Furthermore, adjuvant therapies including radiation and chemotherapy have high cytotoxicity which causes extensive damage to surrounding healthy tissues and treatment is usually halted before GBM is fully eradicated. Finally, most GBM cases demonstrate temozolomide resistance, a common reason for GBM treatment failure. Therefore, there is an urgent need to develop a suitable alternative therapy that targets GBM specifically and has low cytotoxicity for healthy cells. We previously reported that transient receptor potential melastatin 7 (TRPM7) channels are aberrantly upregulated in GBM, and inhibition of TRPM7 reduced GBM cellular functions including proliferation, migration, and invasion. This suggests TRPM7 is a potential therapeutic target for GBM treatment. In this study, we investigated the effects of the TRPM7 inhibitor, carvacrol, on human GBM cell lines U87 and U251 in vivo. With the use of a flank xenograft GBM mouse model, we demonstrated that carvacrol significantly reduced the tumour size in both mice injected with U87 and U251 cells, decreased p‐Akt protein level and increased p‐GSK3β protein levels. Therefore, these results suggest that carvacrol may have therapeutic potential for GBM treatment. Abstract : Inhibition of TRPM7 by carvacrol reduces tumour growth in a mouse xenograft model of glioblastoma. The effect of carvacrol is potentially through the modulation of PI3K/Akt/GSK3β signalling.