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. Changes in cytosolic superoxide dismutase (SOD1) activity after PDT and the intracellular accumulation of photosensitizers in sensitive and resistant colon cancer cell lines were examined. The photosensitizers' distributions indicate that Ph II could be a potential substrate for P-gp, in contrast to Hyp. We observed an increase in SOD1 activity after PDT for both photosensitizing agents. The changes in SOD1 activity show that photodynamic action generates oxidative stress in the treated cells. P-gp appears to play a role in the intracellular accumulation of Ph II. Therefore the efficacy of PDT on multidrug-resistant cells depends on the affinity of P-gp to the photosensitizer used. The weaker accumulation of photosensitizing agents enhances the antioxidant response, and this could influence the efficacy of PDT.
Saczko
Jolanta
J
Department of Medical Biochemistry, Wrocław Medical University, Wrocław, Poland. michal@bioch.am.wroc.pl
Kulbacka
Julita
J
Chwilkowsa
Agnieszka
A
Pola
Andrzej
A
Lugowski
Mateusz
M
Marcinkowska
Anna
A
Malarska
Anna
A
Banas
Teresa
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000873:Anthracenes; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D017323:Dihematoporphyrin Ether / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000873:Anthracenes; D017319:Photosensitizing Agents; D010569:Perylene; C004965:hypericin; D017323:Dihematoporphyrin Ether; D013482:Superoxide Dismutase