Mechanism of a new photosensitizer (TBZPy) in the treatment of high-risk human papillomavirus-related diseases.

Abstract

BACKGROUND\nHigh-risk human papillomavirus infection is closely related to the development of several diseases, including cervical cancer and condyloma acuminatum. We recently designed a new photosensitizer, 1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin-1-ium iodide salt (TBZPy), which shows good photodynamic properties. In this study, we explored the mechanism of action of the TBZPy photosensitizer and its potential application in the treatment of high-risk human papillomavirus-related diseases.\n\n\nMETHODS\nHeLa cells (infected by the high-risk human papillomavirus strain HPV18) were treated with TBZPy-photodynamic therapy (PDT). Cell viability, production of reactive oxygen species, apoptosis, and mitochondrial membrane depolarization were evaluated using cell counting kit-8, immunofluorescence, and flow cytometry assays, respectively. Expression levels of the anti-apoptotic proteins Bcl-2 and Bcl-XL; pro-apoptotic proteins Bax, cytochrome C, cleaved caspase 3, and cleaved caspase 9; and the mitochondrial stress protein heat shock protein 60 were examined by western blotting.\n\n\nRESULTS\nTBZPy-PDT inhibited the viability and promoted reactive oxygen species production, lactate dehydrogenase release, and apoptosis of HeLa cells in vitro. TBZPy-PDT also promoted the loss of mitochondrial membrane potential, downregulated the expression of anti-apoptotic proteins, and upregulated the expression of pro-apoptotic proteins. Moreover, TBZPy-PDT downregulated the expression of the human papillomavirus E6 and E7 proteins.\n\n\nCONCLUSION\nOur study demonstrates the effectiveness of TBZPy-PDT against human papillomavirus-related diseases. These findings provide a foundation for using this novel photosensitizer to treat diseases associated with high-risk human papillomavirus infection.