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A Photodynamic Approach to Study Function of Intracellular Vesicle Rupture
Published on: March 17, 2023
Ascorbate and endocytosed Motexafin gadolinium induce lysosomal rupture
Carsten Berndt1, Tino Kurz, Sarah Bannenberg
1Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Cancer Letters
|April 16, 2011
Summary
Motexafin gadolinium (MGd) enters cancer cells via clathrin-dependent endocytosis, leading to lysosomal damage and apoptosis. This mechanism explains how MGd enhances radiation therapy in malignant cells.
Area of Science:
- Oncology
- Cell Biology
- Radiotherapy
Background:
- Motexafin gadolinium (MGd) is an anti-cancer agent that sensitizes malignant cells to ionizing radiation.
- The precise mechanisms of MGd uptake and its radiosensitizing effects remain largely unknown.
Purpose of the Study:
- To elucidate the cellular uptake pathways of Motexafin gadolinium.
- To investigate the mechanisms by which MGd enhances the efficacy of ionizing radiation in cancer cells.
Main Methods:
- Investigated MGd uptake using endocytosis pathway assays.
- Assessed lysosomal membrane integrity following MGd treatment.
- Evaluated the role of reactive oxygen species (ROS) in MGd-induced cellular effects.
- Examined the synergistic effects of MGd and irradiation on cancer cell apoptosis.
Main Results:
- MGd is internalized by cancer cells through clathrin-dependent endocytosis.
- MGd induces lysosomal membrane permeabilization, likely mediated by ROS.
- High MGd concentrations synergize with irradiation to induce apoptosis in cancer cells, particularly those with high endocytic activity.
Conclusions:
- The study reveals that MGd's anti-cancer activity involves clathrin-mediated endocytosis and lysosomal disruption.
- ROS generation and subsequent apoptosis are key components of MGd's synergistic effect with radiation.
- These findings offer critical insights into the mode of action of MGd, a drug currently in clinical trials.
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