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Mitochondrial alterations in photodynamic therapy-resistant cells
S M Sharkey1, B C Wilson, R Moorehead
1Ontanio Cancer Foundation, Hamilton Regional Cancer Centre, Canada.
Cancer Research
|October 15, 1993
Summary
Radiation-induced fibrosarcoma cells (RIF-8A) selected for resistance to photodynamic therapy (PDT) exhibit distinct mitochondrial differences compared to sensitive RIF-1 cells. These structural and functional mitochondrial changes likely contribute to PDT resistance.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Photodynamic therapy (PDT) is a cancer treatment modality.
- Resistance to PDT can develop in cancer cells.
- Mitochondria are key targets in PDT.
Purpose of the Study:
- To characterize radiation-induced fibrosarcoma cells (RIF-8A) selected for resistance to Photofrin-mediated PDT.
- To compare mitochondrial morphology and function between PDT-resistant (RIF-8A) and PDT-sensitive (RIF-1) cells.
Main Methods:
- Electron microscopy for mitochondrial morphology assessment.
- Measurement of ATP production and succinate dehydrogenase activity.
- Analysis of oxygen consumption rates.
- 2-deoxy-D-glucose survival curves to assess glycolytic inhibition susceptibility.
Main Results:
- RIF-8A cells showed smaller mitochondria with higher cristae density and denser staining compared to RIF-1 cells.
- RIF-8A cells produced more ATP and had higher succinate dehydrogenase activity, but similar oxygen consumption rates as RIF-1 cells.
- RIF-1 cells were more susceptible to glycolytic inhibition by 2-deoxy-D-glucose.
Conclusions:
- Significant differences in mitochondrial structure and function exist between PDT-resistant (RIF-8A) and PDT-sensitive (RIF-1) cells.
- Altered mitochondrial energy metabolism may play a role in Photofrin-mediated PDT resistance.
- These findings suggest potential therapeutic strategies targeting mitochondrial function in PDT-resistant cancers.