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.

Development of biodegradable nanogels for lipase accelerated drug release of 5-aminolevulinic acid

“…The PpIX converted from 5-ALA in fibroblasts was rapidly converted into heme by ferrous chelatase, which greatly reduces the effect of PDT. The lack of ferrous chelatase in cancer cells leads to a large accumulation of PpIX [25] . When the concentration of 5-ALA was greater than or equal to 2 mM, the PDT effect reached equilibrium, which agreed to the published research results [26] .…”