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Journal of Cancer Research and Clinical Oncology

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10-04-2023 | Research

The adverse effect of anticancer drug toremifene on vascular smooth muscle cells is an important aspect of its tumor growth inhibition

Authors: Huiyun Wang, Juan Liu, Mingxing Wang, Chun Yang, Guixue Wang, Tingzhang Hu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2023

Abstract

Purpose

Toremifene (TOR) is widely used as an antineoplastic drug and has an inhibitory effect on angiogenesis in mesenteric desmoid tumors and vascular intracranial solitary fibrous tumors. However, no study has investigated the direct effect of TOR on vascular cells. This study aimed at exploring the effect of TOR on the behaviors of vascular smooth muscle cells (VSMCs).

Methods

Human aortic umbilical vascular smooth muscle cells (HAVSMCs) were treated by TOR. Cell morphology, migration, adhesion, and proliferation assay were investigated. The cell cycle, apoptosis, mitochondrial membrane potential, and reactive oxygen species were assessed using flow cytometry. Caspase-3 and 9 activities were assayed using Caspase-3 and Caspase-9 Activity Assay kits, respectively. Immunofluorescence and Western blot assays were carried out to characterize protein expressions of PCNA, p53, and Rho/ROCK signaling pathway.

Results

TOR damaged cytoskeleton, inhibited VSMC proliferation, migration, and adhesion, and induced abnormal cell morphology and apoptosis. The antiproliferative activity of TOR was associated with the induction of G₀/G₁ phase arrest, blocking the cell cycle. TOR disrupted intracellular reactive oxygen species and mitochondrial membrane potential, and enhanced p53 expression and the activities of caspase-3 and caspase-9. Thus, TOR-induced apoptosis by the mitochondrial signaling pathway. Additionally, TOR induced decreased Rho, ROCK, MLC, and pMLC proteins. Collectively, TOR may affect multiple behaviors of VSMCs by damaging cytoskeleton through the Rho/ROCK pathway.

Conclusion

The adverse effect of TOR on VSMCs could be considered as an important aspect of tumor growth inhibition.

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Title: The adverse effect of anticancer drug toremifene on vascular smooth muscle cells is an important aspect of its tumor growth inhibition
Authors: Huiyun Wang
Juan Liu
Mingxing Wang
Chun Yang
Guixue Wang
Tingzhang Hu
Publication date: 10-04-2023
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2023
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-023-04744-9

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