Alectinib combined with 5-aminolevulinic acid-based photodynamic therapy promotes apoptosis in endometrial cancer cells by targeting ferrochelatase - Report - MDSpire
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Alectinib combined with 5-aminolevulinic acid-based photodynamic therapy promotes apoptosis in endometrial cancer cells by targeting ferrochelatase
Combination of Alectinib and 5-Aminolevulinic Acid-Based Photodynamic Therapy Enhances Apoptosis in Endometrial Cancer Cells by Inhibiting Ferrochelatase Activity
Overview
This study investigates the combined effect of alectinib and 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) on endometrial cancer cells, revealing that alectinib enhances the efficacy of ALA-PDT by inhibiting ferrochelatase activity. The combination treatment significantly increases apoptosis rates in endometrial cancer cells compared to either treatment alone.
Background
Endometrial cancer is a prevalent malignancy among women, often treated with hysterectomy, which carries surgical risks. Photodynamic therapy (PDT) is a promising alternative that utilizes photosensitizers to generate reactive oxygen species (ROS) for tumor cell destruction. However, the effectiveness of PDT can be limited by the activity of ferrochelatase (FECH), which converts protoporphyrin IX (PpIX) into heme, reducing PpIX accumulation necessary for effective PDT.
Combination treatment of alectinib and ALA-PDT enhances intracellular ROS generation.
Flow cytometry indicates a higher apoptosis rate with combined treatment compared to ALA-PDT or alectinib alone.
Alectinib treatment increases FECH mRNA and protein expression levels.
PpIX co-localizes with mitochondria, indicating effective targeting of tumor cells.
Clinical Implications
The findings suggest that alectinib may serve as an adjunct to ALA-PDT in endometrial cancer treatment by enhancing apoptosis through FECH inhibition.
Conclusion
The study demonstrates that alectinib enhances the antitumor effects of ALA-PDT in endometrial cancer cells by targeting FECH, leading to increased apoptosis and ROS accumulation.