Methadone enhances the effectiveness of 5‐aminolevulinic acid‐based photodynamic therapy for squamous cell carcinoma and glioblastoma in vitro

• Published in: Journal of biophotonics Vol. 12; no. 10; pp. e201800468 - n/a
• Main Authors: Shi, Lei, Buchner, Alexander, Pohla, Heike, Pongratz, Thomas, Rühm, Adrian, Zimmermann, Wolfgang, Gederaas, Odrun A., Zhang, Linglin, Wang, Xiuli, Stepp, Herbert, Sroka, Ronald
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH & Co. KGaA 01.10.2019; Wiley Subscription Services, Inc
• Subjects: 5‐aminolevulinic acid‐based photodynamic therapy (ALA‐PDT); Aminolevulinic acid; Analgesics; Apoptosis; Biotechnology; Brain cancer; Cell cycle; cell cycle phase; Cell survival; Chemotherapy; Cytotoxicity; Fluorescence; G1 phase; Glioblastoma; Methadone; Photodynamic therapy; Protoporphyrin; Protoporphyrin IX; Squamous cell carcinoma; squamous cell carcinoma (SCC); Survival; Tumors; 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT); apoptosis; glioblastoma; cell cycle phase; squamous cell carcinoma (SCC); methadone
• ISSN: 1864-063X; 1864-0648
• DOI: 10.1002/jbio.201800468

Although having shown promising clinical outcomes, the effectiveness of 5‐aminolevulinic acid‐based photodynamic therapy (ALA‐PDT) for squamous cell carcinoma (SCC) and glioblastoma remains to be improved. The analgesic drug methadone is able to sensitize various tumors to chemotherapy. In this in vitro study, the influence of methadone to the effectiveness of ALA‐PDT for SCC (FADU) and glioblastoma (A172) was investigated on the protoporphyrin IX (PpIX) fluorescence, survival rates, apoptosis, and cell cycle phase, each with or without the presence of methadone. The production of PpIX was increased by methadone in FADU cells while it was decreased in A172 cells. The survival rates of both cell lines treated by ALA‐PDT were significantly reduced by the combination with methadone (P < .05). Methadone also significantly increased the percentage of apoptotic cells and improved the effect of ALA‐PDT on the cell cycle phase arrest in the G0/G1 phase (P < .05). This study demonstrates the potential of methadone to influence the cytotoxic effect of ALA‐PDT for both SCC and glioblastoma cell lines. The effectiveness of 5‐aminolevulinic acid‐based photodynamic therapy (ALA‐PDT) for squamous cell carcinoma (SCC) and glioblastoma needs to be improved. Our investigations showed for the first time that the analgesic drug methadone promotes ALA‐PDT for both SCC and glioblastoma by activation of apoptosis pathways and increased cell cycle arrest in vitro (P < .05), which mightily contributes to establish a novel PDT protocol being less painful and more effective for cancer treatment.