Cytosolic superoxide dismutase activity after photodynamic therapy, intracellular distribution of Photofrin II and hypericin, and P-glycoprotein localization in human colon adenocarcinoma.

In photodynamic therapy (PDT), a tumor-selective photosensitizer is administered and then activated by exposure to a light source of applicable wavelength. Multidrug resistance (MDR) is largely caused by the efflux of therapeutics from the tumor cell by means of P-glycoprotein (P-gp), resulting in reduced efficacy of the anticancer therapy. This study deals with photodynamic therapy with Photofrin II (Ph II) and hypericin (Hyp) on sensitive and doxorubicin-resistant colon cancer cell lines.

Uptake of photofrin II, a photosensitizer used in photodynamic therapy, by tumour cells in vitro.

Photosensitizing dyes are used in fluorescence diagnostics and photodynamic therapy (PDT). These usually hematoporphyrin derivatives (HpD) accumulate preferentially within neoplastic tissues. HpD is a mixture of ether and ester linked porphyrins.

Photofrin--factor of photodynamic therapy induces apoptosis and necrosis.

Photodynamic therapy (PDT) causes irreversible photodamage of tumor and other malignant tissues. The effect of reactive oxygen species generation in the presence of photofrin (HpD) was studied. The studies were performed on endothelial cell line from foetal aorta of calves and on normal fibroblasts cell line (3T3 -Balb) and also on malignant line (A431).

The structure of P-glycoprotein and the secretion of lysosomal enzymes in multidrug-resistant cells.

We have previously demonstrated that multidrug-resistant cells have a lower content of lysosomal enzymes, a consequence of an increased rate of secretion. The question was therefore to know whether an intact functional P-glycoprotein was necessary for expression of this property. Control NIH3T3 and mdr1-gene-transfected cells (pHaMDR1) were used together with 2 variants either lacking 23 amino acids at the carboxyl terminal (pHaMDRC 23) or in which 4 extra amino acids are inserted (pHaMDRBL2).

Increased accumulation of drugs in multidrug-resistant cells induced by liposomes.

A multidrug-resistant cell such as the human lymphoblastic leukemic cell CEM/VLB100 accumulates far less vinblastine (VLB) than its drug-sensitive parent, CEM. When CEM/VLB100 cells are exposed to liposomes consisting of the phospholipids cardiolipin, dioleoylphosphatidic acid, or phosphatidylinositol bearing unsaturated fatty acids and then tested for uptake of VLB, accumulation of drug rapidly rises to levels approaching those of CEM cells, which are relatively unaffected by the liposome treatment. The liposomes are not carriers of entrapped drug.