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Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis.
Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis.
- Source :
-
Radiation research [Radiat Res] 2005 Sep; Vol. 164 (3), pp. 250-7. - Publication Year :
- 2005
-
Abstract
- The anti-malarial drug chloroquine (CQ) is also thought to be a potential radiation sensitizer. To gain a better understanding of how the lysomotropic CQ can potentiate the effects of ionizing radiation, we investigated the effects of CQ on lysosomal and mitochondrial membrane stability, the subcellular localization of ceramide, plasma membrane permeability, and the mode of cell death in response to irradiation. We found that CQ accumulated in the lysosomes and thus lysosomal volumes increased. As a result, both the lysosomal and plasma membranes were destabilized. After 7 Gy irradiation, most ceramide was associated with the lysosomes in the cells treated with CQ but not in the CQ-untreated control. The elevated levels of ceramide in the lysosomes of the CQ-treated cells appeared to further destabilize the lysosomal and plasma membranes of the cell. Both CQ-treated and -untreated cells had approximately the same rate of cell death by apoptosis after 7 Gy irradiation (P > 0.05, ns). However, in contrast to the CQ-untreated control, the CQ-treated cells underwent massive cell death by necrosis at 24-48 h after irradiation (P < 0.05). Taken together, our data support the idea that the increase in cytotoxic effects by the combination of CQ and radiation is due to radiation-mediated apoptosis and CQ-mediated necrosis.
- Subjects :
- Apoptosis radiation effects
Cell Line, Tumor
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Humans
Intracellular Membranes pathology
Lysosomes pathology
Membrane Fluidity drug effects
Membrane Fluidity radiation effects
Necrosis pathology
Radiation Dosage
Radiation-Sensitizing Agents administration & dosage
Apoptosis drug effects
Breast Neoplasms pathology
Chloroquine administration & dosage
Intracellular Membranes drug effects
Intracellular Membranes radiation effects
Lysosomes drug effects
Lysosomes radiation effects
Radiation Tolerance drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0033-7587
- Volume :
- 164
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Radiation research
- Publication Type :
- Academic Journal
- Accession number :
- 16137197
- Full Text :
- https://doi.org/10.1667/rr3436.1