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Blocking of Transient Receptor Potential Vanilloid 1 (TRPV1) promotes terminal mitophagy in multiple myeloma, disturbing calcium homeostasis and targeting ubiquitin pathway and bortezomib-induced unfolded protein response by Beider, Katia; Rosenberg, Evgenia; Dimenshtein-Voevoda, Valeria; Sirovsky, Yaarit; Vladimirsky, Julia; Magen, Hila; Ostrovsky, Olga; Shimoni, Avichai; Bromberg, Zohar; Weiss, Lola; Peled, Amnon; Nagler, Arnon is a Medicine article available to read on EtoBox.

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## Abstract ## Background Chemoresistance remains a major treatment obstacle in multiple myeloma (MM). Novel new therapies are thus in need. Transient Receptor Potential Vanilloid type 1 (TRPV1) is a calcium-permeable ion channel that has been demonstrated to be expressed in solid tumors. Calcium channels have been shown to be involved in the regulation of cell proliferation, chemoresistance, migration and invasion. The aim of the current study was to evaluate its possible role in MM. ## Methods Pharmacological inhibitor was used to evaluate the role of TRPV1 in MM cell lines and primary MM cells. Flow cytometry, molecular analysis, fluorescent microscopy, proteomic analysis and xenograft in vivo model of MM with BM involvement were employed to assess the effect of TRPV1 inhibition and decipher its unique mechanism of action in MM. ## Results TRPV1 was found to be expressed by MM cell lines and primary MM cells. TRPV1 inhibition using the antagonist AMG9810-induced MM cell apoptosis and synergized with bortezomib, overcoming both CXCR4-dependent stroma-mediated and acquired resistance. In accordance, AMG9810 suppressed the expression and activation of CXCR4 in MM cells. TRPV1 inhib

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Author

Beider, Katia; Rosenberg, Evgenia; Dimenshtein-Voevoda, Valeria; Sirovsky, Yaarit; Vladimirsky, Julia; Magen, Hila; Ostrovsky, Olga; Shimoni, Avichai; Bromberg, Zohar; Weiss, Lola; Peled, Amnon; Nagler, Arnon

Publisher

BioMed Central; Springer (Biomed Central Ltd.); London: BioMed Central, 2008-; Springer Science and Business Media LLC (ISSN 1756-8722)

Published

2020

Language

EN

Field

Medicine (Health Sciences)