Related Experiment Videos
Photofrin and light induces microtubule depolymerization in cultured human endothelial cells
1Department of Medicine, University of Rochester School of Medicine and Dentistry, New York 14642.
Cancer Research
|June 15, 1992
Summary
Photodynamic therapy with Photofrin causes dose-dependent microtubule (MT) depolymerization in endothelial cells. This transient effect, linked to calcium increase, occurs without significant cell death, potentially impacting vascular integrity.
Area of Science:
- Cell Biology
- Photodynamic Therapy
- Vascular Biology
Background:
- Microtubules (MT) are crucial for maintaining endothelial cell shape and vascular integrity.
- Photodynamic therapy (PDT) utilizes photosensitizers and light to induce cell death.
- The effects of PDT on endothelial cell MT stability are not fully understood.
Purpose of the Study:
- To investigate the impact of photodynamic insult on endothelial cell microtubule (MT) status.
- To determine the relationship between MT depolymerization, cellular ATP levels, and cell viability following PDT.
- To explore the potential mechanisms and consequences of PDT-induced MT disruption in endothelial cells.
Main Methods:
- Human umbilical vein endothelial cells were incubated with the photosensitizer Photofrin.
- Cells were exposed to light, and microtubule (MT) depolymerization was assessed using immunofluorescence microscopy and alpha-tubulin antibody.
- Cellular ATP levels and cell viability (trypan blue exclusion) were monitored post-irradiation.
Main Results:
- A light dose-dependent depolymerization of cytoplasmic microtubules (MT) was observed as early as 15 minutes after irradiation.
- At sublethal light doses, MT depolymerization was transient, with repolymerization occurring within 2-3 hours.
- No correlation was found between MT depolymerization and cellular ATP levels; viability remained largely unaffected at doses causing transient MT disruption.
Conclusions:
- Photodynamic insult causes transient microtubule (MT) depolymerization in endothelial cells, likely due to increased intracellular calcium.
- This effect occurs at photodynamic doses that do not significantly decrease cell viability.
- Disruption of endothelial MT by PDT may alter vascular permeability and expose the thrombogenic subendothelium, with implications for therapeutic outcomes.