RRC ID 59874
Author Yamamoto S, Yamashita T, Ito M, Caaveiro JMM, Egashira N, Tozaki-Saitoh H, Tsuda M.
Title New pharmacological effect of fulvestrant to prevent oxaliplatin-induced neurodegeneration and mechanical allodynia in rats.
Journal Int J Cancer
Abstract Oxaliplatin, which is widely used as chemotherapy for certain solid cancers, frequently causes peripheral neuropathy. Commonly described neuropathic symptoms include aberrant sensations such as mechanical allodynia (hypersensitivity to normally innocuous stimuli). Although oxaliplatin neuropathy is a dose-limiting toxicity, there are no established preventive strategies available at present. By screening several sets of small-molecule chemical libraries (more than 3,000 compounds in total) using a newly established in vitro high-throughput phenotypic assay, we identified fulvestrant, a clinically approved drug for the treatment of breast cancer in postmenopausal women, as having a protective effect on oxaliplatin-induced neuronal damage. Furthermore, histological and behavioural analyses using a rat model of oxaliplatin neuropathy demonstrated the in vivo efficacy of fulvestrant to prevent oxaliplatin-induced axonal degeneration of the sciatic nerve and mechanical allodynia. Furthermore, fulvestrant did not interfere with oxaliplatin-induced cytotoxicity against cancer cells. Thus, our findings reveal a previously unrecognised pharmacological effect of fulvestrant to prevent oxaliplatin-induced painful peripheral neuropathy without impairing its cytotoxicity against cancer cells and may represent a novel prophylactic option for patients receiving oxaliplatin chemotherapy.
Volume 145(8)
Pages 2107-2113
Published 2019-10-15
DOI 10.1002/ijc.32043
PMID 30515800
MeSH Animals Cell Line Fulvestrant / pharmacology* Hybridomas Hyperalgesia / chemically induced Hyperalgesia / prevention & control* Male Mice Neurons / drug effects* Neurons / pathology Neuroprotective Agents / pharmacology Oxaliplatin Peripheral Nervous System Diseases / chemically induced Peripheral Nervous System Diseases / prevention & control* Rats, Sprague-Dawley
IF 4.982
Times Cited 1
Human and Animal Cells Colon-26(RCB2657)