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

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.

• Authors: Bernhard Gillissen, Antje Richter, Frank Essmann, Wolfgang Kemmner
• Journal: BMC cancer (BMC Cancer) Vol. 21 Issue 1 Pg. 971 (Aug 30 2021) ISSN: 1471-2407 [Electronic] England
• PMID: 34461853 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Carbazoles
• Photosensitizing Agents
• Piperidines
• Protoporphyrins
• Aminolevulinic Acid
• protoporphyrin IX
• alectinib

Topics

• Aminolevulinic Acid (pharmacology)
• Carbazoles (pharmacology)
• Fluorescence
• Humans
• Light
• Neoplasms (drug therapy, pathology)
• Photochemotherapy (methods)
• Photosensitizing Agents (pharmacology)
• Piperidines (pharmacology)
• Protoporphyrins (metabolism)
• Tumor Cells, Cultured