Methadone-Not a magic bullet in melanoma therapy.

Abstract

Methadone (Met) mainly acts as a μ-opioid receptor agonist. Recent evidence pointing towards the role of Met in sensitization of certain cancer cell lines to chemotherapeutic agents has promoted the hypothesis that Met may be a useful adjuvant to cancer chemotherapy. We wanted to address whether Met has, alone or in combination with a chemotherapeutic agent, an effect on melanoma cell viability in vitro. Only a small fraction (4.3%) of our 102 melanoma biobank cell lines with RNA-sequencing data showed expression of the main receptor for Met (OPRM1). We assessed the viability of melanoma cell lines with high, medium or low/no OPRM1 expression (OPRM1high , OPRM1med , OPRM1neg ) 72 hours after treatment with Met alone or combined with cisplatin (Cis). Our analyses show that Met alone did not affect cell viability. While Cis/Met treatment did not have an effect on viability of OPRM1med or OPRM1neg cell lines, it resulted in a slightly decreased cell viability of OPRM1high cells. Clinically, concurrent temozolomide/Met treatment did not have an effect in our single-case report of a patient suffering from uveal melanoma. Taken together, our findings do not provide evidence for recommending Met as an adjuvant to chemotherapy in patients with melanoma.

• Authors: Marie-Charlotte Brüggen, Joanna Mangana, Anja Irmisch, Lars E French, Mitchell P Levesque, Phil F Cheng, Reinhard Dummer
• Journal: Experimental dermatology (Exp Dermatol) Vol. 27 Issue 6 Pg. 694-696 (06 2018) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 29577418 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents
• OPRM1 protein, human
• Receptors, Opioid, mu
• Cisplatin
• Methadone
• Temozolomide

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin (pharmacology)
• Drug Screening Assays, Antitumor
• Fatal Outcome
• Gene Expression
• Humans
• Melanoma (drug therapy, genetics)
• Methadone (pharmacology, therapeutic use)
• Middle Aged
• Receptors, Opioid, mu (agonists, genetics)
• Skin Neoplasms (drug therapy, genetics)
• Temozolomide (therapeutic use)
• Uveal Neoplasms (drug therapy)