MAL-PDT inhibits oral precancerous cells and lesions via autophagic cell death

Yen Yun Wang, Yuk Kwan Chen, Chu Sung Hu, Ling Yi Xiao, Wan Ling Huang, Tsung Chen Chi, Kuang Hung Cheng, Yun Ming Wang*, Shyng Shiou F. Yuan

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Oral cancer is a common cancer with a high mortality rate. While surgery is the most effective treatment for oral cancer, it frequently causes deformity and dysfunction in the orofacial region. In this study, methyl aminolevulinate photodynamic therapy (MAL-PDT) as a prevention tool against progression of precancerous lesion to oral cancer was explored. Methods: For in vitro studies, we evaluated the effects of MAL-PDT on viability of DOK oral precancerous cells by XTT, cell morphology by TEM, and intracellular signaling pathways by flow cytometry, Western blotting, and immunofluorescence. For in vivo study, DMBA was used to induce oral precancerous lesions in hamsters followed by MAL-PDT treatment. We measured tumor size and body weight weekly. After sacrifice, buccal pouch lesions were processed for H&E stain and immunohistochemistry analysis. Results: MAL-PDT induced autophagic cell death in DOK oral precancerous cells. The autophagy-related markers LC3II and p62/SQSTM1 and autophagosome formation in DOK cells were increased after MAL-PDT treatment. In vivo, Metvix ® -PDT treatment decreased tumor growth and enhanced LC3II expression in hamster buccal pouch tumors induced by DMBA. Conclusions: Our in vitro and in vivo results suggest that MAL-PDT may provide an effective therapy for oral precancerous lesions through induction of autophagic cell death.

Original languageEnglish
Pages (from-to)758-771
Number of pages14
JournalOral Diseases
Volume25
Issue number3
DOIs
StatePublished - Apr 2019

Keywords

  • autophagy
  • methyl aminolevulinate
  • oral cancer
  • oral precancerous lesion
  • photodynamic therapy

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    Wang, Y. Y., Chen, Y. K., Hu, C. S., Xiao, L. Y., Huang, W. L., Chi, T. C., Cheng, K. H., Wang, Y. M., & Yuan, S. S. F. (2019). MAL-PDT inhibits oral precancerous cells and lesions via autophagic cell death. Oral Diseases, 25(3), 758-771. https://doi.org/10.1111/odi.13036