Next Article in Journal
Sex Differences in Biological Systems and the Conundrum of Menopause: Potential Commonalities in Post-Menopausal Disease Mechanisms
Previous Article in Journal
Role of Polymer Concentration and Crosslinking Density on Release Rates of Small Molecule Drugs
Article

Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer

1
Department of Molecular and Translational Oncology, Maria Skłodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
2
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland
3
Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, Pawińskiego 5a, 02-106 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Deceased.
Academic Editors: Dorota Wrześniok and Jakub Rok
Int. J. Mol. Sci. 2022, 23(8), 4117; https://doi.org/10.3390/ijms23084117
Received: 1 March 2022 / Revised: 4 April 2022 / Accepted: 6 April 2022 / Published: 8 April 2022
(This article belongs to the Special Issue Irradiation and Anti-cancer Therapies: Future and Challenges)
Photodynamic therapy (PDT) is a valuable treatment method for vulvar intraepithelial neoplasia (VIN). It allows for the treatment of a multifocal disease with minimal tissue destruction. 5-Aminolevulinic acid (5-ALA) is the most commonly used prodrug, which is converted in the heme pathway to protoporphyrin IX (PpIX), an actual photosensitizer (PS). Unfortunately, not all patients treated with PDT undergo complete remission. The main cause of their failure is resistance to anticancer therapy. In many cancers, resistance to various anticancer treatments is correlated with increased activity of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1). Enhanced activity of drug pumps may also affect the effectiveness of therapy. To investigate whether multidrug resistance mechanisms underlie PDT resistance in VIN, porphyrins were isolated from sensitive and resistant vulvar cancer cells and their culture media. APE1 activity was measured, and survival assay after PDT combined with APE1 inhibitor was performed. Our results revealed that resistant cells accumulated and effluxed less porphyrins than sensitive cells, and in response to PDT, resistant cells increased APE1 activity. Moreover, PDT combined with inhibition of APE1 significantly decreased the survival of PDT-resistant cells. This means that resistance to PDT in vulvar cancer may be the result of alterations in the heme synthesis pathway. Moreover, increased APE1 activity may be essential for the repair of PDT-mediated DNA damage, and inhibition of APE1 activity may increase the efficacy of PDT. View Full-Text
Keywords: photodynamic therapy; photosensitizer; protoporphyrin IX; heme metabolism; multidrug resistance; DNA repair; APE1; combined therapy; APE1 inhibitor photodynamic therapy; photosensitizer; protoporphyrin IX; heme metabolism; multidrug resistance; DNA repair; APE1; combined therapy; APE1 inhibitor
Show Figures

Figure 1

MDPI and ACS Style

Mossakowska, B.J.; Shahmoradi Ghahe, S.; Cysewski, D.; Fabisiewicz, A.; Tudek, B.; Siedlecki, J.A. Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer. Int. J. Mol. Sci. 2022, 23, 4117. https://doi.org/10.3390/ijms23084117

AMA Style

Mossakowska BJ, Shahmoradi Ghahe S, Cysewski D, Fabisiewicz A, Tudek B, Siedlecki JA. Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer. International Journal of Molecular Sciences. 2022; 23(8):4117. https://doi.org/10.3390/ijms23084117

Chicago/Turabian Style

Mossakowska, Beata J., Somayeh Shahmoradi Ghahe, Dominik Cysewski, Anna Fabisiewicz, Barbara Tudek, and Janusz A. Siedlecki. 2022. "Mechanisms of Resistance to Photodynamic Therapy (PDT) in Vulvar Cancer" International Journal of Molecular Sciences 23, no. 8: 4117. https://doi.org/10.3390/ijms23084117

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop