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Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin

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Item Type:Article
Title:Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin
Creators Name:Gillissen, B. and Richter, A. and Essmann, F. and Kemmner, W.
Abstract:BACKGROUND: Photodynamic therapy with a photosensitizer such as protoporphyrin-IX, a light sensitive metabolite of heme synthesis, is a highly selective treatment for various carcinomas. In previous studies, we found a significant down regulation of the relevant enzyme ferrochelatase in gastrointestinal carcinomas leading to an accumulation of protoporphyrin-IX within the tumor cells. Recent studies showed that a novel anti-cancer drug, Alectinib, an orally available, highly selective, potent second-generation inhibitor of anaplastic lymphoma tyrosinkinase binds to ferrochelatase. Therefore, we were interested to see whether Alectinib treatment might lead to an accumulation of protoporphyrin IX. METHODS: Tumor cells of different origin were cultured, treated with LED-light and Alectinib. Results were gained by flow cytometry, immunohistochemistry and western blotting. Apoptosis was determined by flow cytometric analysis of Annexin V-FITC stained cells. In addition, cells were counterstained with propidium iodide to distinguish early apoptotic cells and late apoptotic/necrotic cells. RESULTS: Here, we report that photodynamic treatment of tumor cell lines of different origin in combination with Alectinib increased protoporphyrin-IX specific fluorescence and concomitantly cell death. CONCLUSIONS: The usage of Alectinib could be another step for enhancing the effectiveness of photodynamic therapy. Further experiments will show whether photodynamic therapy in combination with Alectinib could be a new strategy for the treatment of e.g. peritoneal disseminated carcinomas.
Keywords:Photodynamic Therapy, Protoporphyrin-IX, Ferrochelatase, Alectinib, Gastrointestinal Carcinomas
Source:BMC Cancer
Publisher:BioMed Central
Page Range:971
Date:30 August 2021
Official Publication:https://doi.org/10.1186/s12885-021-08667-x
PubMed:View item in PubMed

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