Comparative sensitivity of microvascular endothelial cells, fibroblasts and tumor cells after in vitro photodynamic therapy with meso-tetra-hydroxyphenyl-chlorin.

Abstract

The phototoxic effect of meso-tetra-hydroxyphenyl-chlorin (mTHPC)-mediated photodynamic therapy (PDT) on human microvascular endothelial cells (hMVEC) was compared with that on human fibroblasts (BCT-27) and two human tumor cell lines (HMESO-1 and HNXOE). To examine the relationship between intrinsic phototoxicity and intracellular mTHPC content, we expressed cell survival as a function of cellular fluorescence. On the basis of total cell fluorescence, HNXOE tumor cells were the most sensitive and BCT-27 fibroblasts the most resistant, but these differences disappeared after correcting for cell volume. Endothelial cells were not intrinsically more sensitive to mTHPC-PDT than tumor cells or fibroblasts. Uptake of mTHPC in hMVEC increased linearly to at least 48 h, whereas drug uptake in the other cell lines reached a maximum by 24 h. No difference in drug uptake was seen between the cell lines during the first 24 h, but by 48 h hMVEC had a 1.8- to 2.8-fold higher uptake than other cell lines. Endothelial cells showed a rapid apoptotic response after mTHPC-mediated PDT, whereas similar protocols gave a delayed apoptotic or necrotic like response in HNXOE. We conclude that endothelial cells are not intrinsically more sensitive than other cell types to mTHPC-mediated PDT but that continued drug uptake beyond 24 h may lead to higher intracellular drug levels and increased photosensitivity under certain conditions.

• Authors: Martijn Triesscheijn, Marjan Ruevekamp, Maurice Aalders, Paul Baas, Fiona A Stewart
• Journal: Photochemistry and photobiology (Photochem Photobiol) 2004 Sep-Oct Vol. 80 Issue 2 Pg. 236-41 ISSN: 0031-8655 [Print] United States
• PMID: 15362947 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Mesoporphyrins
• Photosensitizing Agents
• temoporfin

Topics

• Antineoplastic Agents (chemistry, pharmacology, toxicity)
• Cell Line
• Cell Survival (drug effects, radiation effects)
• Endothelial Cells (drug effects, radiation effects)
• Fibroblasts (drug effects, radiation effects)
• Humans
• Mesoporphyrins (chemistry, pharmacology, toxicity)
• Neoplasms (pathology)
• Photochemotherapy
• Photosensitizing Agents (chemistry, pharmacology, toxicity)
• Time Factors