Riluzole: A neuroprotective drug with potential as a novel anti‑cancer agent (Review)

Abstract

Riluzole, a glutamate release inhibitor, has been in use for the treatment of amyotrophic lateral sclerosis for over two decades since its approval by the Food and Drug Administration. Recently, riluzole has been evaluated in cancer cells and indicated to block cell proliferation and/or induce cell death. Riluzole has been proven effective as an anti-neoplastic drug in cancers of various tissue origins, including the skin, breast, pancreas, colon, liver, bone, brain, lung and nasopharynx. While cancer cells expressing glutamate receptors frequently respond to riluzole treatment, numerous types of cancer cell lacking glutamate receptors unexpectedly responded to riluzole treatment as well. Riluzole was demonstrated to interfere with glutamate secretion, growth signaling pathways, Ca 2+ homeostasis, glutathione synthesis, reactive oxygen species generation and integrity of DNA, as well as autophagic and apoptotic pathways. Of note, riluzole is highly effective in inducing cell death in cisplatin-resistant lung cancer cells. Furthermore, riluzole pretreatment sensitizes glioma and melanoma to radiation therapy. In addition, in triple-negative breast cancer, colorectal cancer, melanoma and glioblastoma, riluzole has synergistic effects in combination with select drugs. In an effort to highlight the therapeutic potential of riluzole, the current study reviewed the effect and outcome of riluzole treatment on numerous cancer types investigated thus far. The mechanism of action and the various molecular pathways affected by riluzole are discussed. Contents 1. Introduction 2. Mechanisms of action of riluzole 3. Riluzole in cancer treatment 4. Conclusion

Targeting patient recovery priorities in degenerative cervical myelopathy: design and rationale for the RECEDE-Myelopathy trial—study protocol

“…Riluzole is an approved neuroprotective drug in clinical use for ALS. It has been linked to reducing glutamatergic excitotoxicity in neurons via a number of mechanisms 83. Although Riluzole treatment did not alter functional outcome in DCM, significant improvements in neck pain were detected 58…”

“…It has been linked to reducing glutamatergic excitotoxicity in neurons via a number of mechanisms. 83 Although Riluzole treatment did not alter functional outcome in DCM, significant improvements in neck pain were detected. 58 A neuropathic pain component in DCM is further supported by recent preclinical findings which echoed the findings of the clinical trial.…”

Glioma‑neuronal interactions in tumor progression: Mechanism, therapeutic strategies and perspectives (Review)

“…The group III receptor antagonists were observed to exert their anti-tumor effects in various types of tumor, including hepatoma, melanoma and non-small-cell lung cancer ( 26 ). Riluzole has been reported to promote apoptosis in glioma cells via antagonizing mGlu3, which results in the suppression of ERK activation ( 27 ). At present, evidence is lacking; however, in terms of whether mGluRs are expressed on neurogliomal synapses, although mGluRs are closely associated with glioma progression, may suggest the involvement of other neuron-glioma interactions.…”

Synthesis and Biological Evaluation of Benzo[d] thiazolyl‐Sulfonyl‐Benzo[4,5]isothiazolo [2,3‐c][1,2,3] triazole Derivatives as EGFR Targeting Anticancer Agents

“…Riluzole a benzo[ d ]thiazole‐containing compound as a glutamate release inhibitor has been in use for the treatment of amyotrophic lateral sclerosis for over two decades since its approval by the Food and Drug Administration. Recently, riluzole has been evaluated in cancer cells and indicated to block cell proliferation and/or induce cell death [10] . Similarly, erlotinib containing a 1,2,3‐triazole derivative also shows robust anticancer activity against diverse NSCLC cells in vitro including PC‐9, H460, H1975, and A549.…”