Publication Type Journal Article
Title Caveolin-1 Modulation Increases Efficacy of a Galacto-Conjugated Phthalocyanine in Bladder Cancer Cells Resistant to Photodynamic Therapy
Authors Patricia M. R. Pereira Belmiro Parada Teresa M. Ribeiro-Rodrigues Carlos A. Fontes-Ribeiro Henrique Girao João P. C. Tomé Rosa Fernandes
Groups CCC
Year 2020
Month June
Volume 17
Number 6
Pages 2145-2154
Abstract Photodynamic therapy (PDT) has demonstrated encouraging anticancer therapeutic results, but the current clinically approved photosensitizers (PSs) are not ideal in the treatment of bladder cancer. Conventional PSs have low selectivity to the bladder tumor tissue and induce toxicity or bystander effects on nontumor urothelium. Previous studies demonstrated that the use of galactose-photosensitizer (PS) conjugates is a more selective method of delivering PDT-mediated toxicity due to their ability to recognize carbohydrate-binding domains overexpressed in bladder tumors. Using patient-derived bladder tumor specimens cultured ex vivo and bladder cancer cell lines with different PDT sensitivity, we find that a galactose-phthalocyanine (PcGal(16)) accumulates in bladder tumors expressing galactose-binding proteins and internalizes through an endorytic process. The endocytosis mechanism is cell line-dependent. In HT-1376 bladder cancer lines resistant to PDT, depletion of caveolin-1-the main structural protein of caveolae structures- increased the amount of sugar-binding proteins, i.e. GLUT1, at the cell membrane resulting in an improved PcGal(16) uptake and PDT efficacy. These data show the potential of ex vivo cultures of bladder cancer, that ideally could mimic the original microenvironment, in screening galacto-PDT agents. Additionally, our studies demonstrate that PDT efficacy in bladder cancer depends on the endocytic mechanisms that regulate PS accumulation and internalization in cancer cells.
Book Title
ISSN 1543-8384
Conference Name
Bibtex ID ISI:000538337600033
Back to Publications List