Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In photodynamic therapy (PDT) a tumor-selective photosensitizer is administered and then activated by exposure to a light source of appropriate wavelength. Multidrug resistance (MDR) is largely caused by the drug efflux from the tumor cell by means of P-glycoprotein, resulting in reduced efficacy of the anticancer therapy. This study deals with photodynamic therapy with Photofrin (Ph) on colon cancer cell lines (doxorubicin-sensitive and -resistant). The cells were treated with 15 and 30 microg/mL Ph and then irradiated by a light dose of 3 or 6 J/cm(2) (632.8 nm). After irradiation the cells were incubated for 0, 3 or 18 h. Crucial factors of oxidative stress (thiobarbituric acid reactive substances [TBARS], protein damage, thiazolyl blue tetrazolium bromide [MTT] assay), changes in cytosolic superoxide dismutase (SOD1) activity after photodynamic reaction (PDR), and the intracellular accumulation of photosensitizers in the cells were examined. Moreover, the expressions of glutathione S-transferase (GST)-pi, a marker protein for photochemical toxicity, and secretory phospholipase A(2), a prognostic and diagnostic marker for colon cancers, were determined. After PDR, increases in SOD1 activity and the level of TBARS were observed in both cell lines. The level of protein-associated -SH groups decreased after PDR. Both cell lines demonstrated stronger GST-pi and PLA(2) expression after PDR, especially after 18 h of incubation. The increasing level of reactive oxygen species following the oxidation of sulfhydryl cell groups and lipid peroxidation influence the activity of many transporters and enzymes. The changes in SOD1 activity show that photodynamic action generates oxidative stress in treated cells. Our study presents that PDR caused oxidative alterations in both examined colon adenocarcinoma cell lines. However, the MDR cells reacted more slowly and all oxidative changes occurred in the delay.
 ...
PMID:Oxidative alterations induced in vitro by the photodynamic reaction in doxorubicin-sensitive (LoVo) and -resistant (LoVoDX) colon adenocarcinoma cells. 2040 24

Electrochemotherapy became one of the therapeutic protocols successfully used in oncology. However, biological effects occurring in cells, especially those which are drug resistant, have not been studied thoroughly. This study presents response of wild and drug resistant breast cancer cells to classical photodynamic therapy with Photofrin or experimental photodynamic therapy with cyanine IR-775, combined with electroporation. Photodynamic reaction or electroporation alone had no cytotoxic effect, but their combination significantly disturbed cellular functions. Applying electroporation allowed the drugs to increase its accumulation, especially for a poorly permeant cyanine in drug resistant cells. FACS analysis showed that even at relatively mild electric field, ca. 90% of cells were permeabilized. High intracellular concentration of drugs triggered the cellular defense system through increased expression of glutathione S-transferase and multidrug resistance proteins (MDR1 and MRP7), particularly in drug resistant cells. Finally, expressively decreased cell metabolism and proliferation, as well as formation of apoptotic bodies and fragmentation of cells were observed after the combined treatment. The results show that electroporation can be used for effective delivery of photosensitizers, even to drug resistant breast cancer cells, which was not tested before. This shows that electro-photodynamic treatment could be a promising approach to overcome a problem of drug resistance in cancer cells.
 ...
PMID:Biological effects in photodynamic treatment combined with electropermeabilization in wild and drug resistant breast cancer cells. 2971 86