Synthesized Pheophorbide a-mediated photodynamic therapy induced apoptosis and autophagy in human oral squamous carcinoma cells

Authors

  • Mee Young Ahn,

    1. Department of Pathology, Research Center for Oral disease Regulation of the Aged, School of Dentistry, Chosun University, Gwangju, Korea
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  • Hyo-Eun Yoon,

    1. Department of Pathology, Research Center for Oral disease Regulation of the Aged, School of Dentistry, Chosun University, Gwangju, Korea
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  • Seong-Min Kwon,

    1. Department of Pathology, Research Center for Oral disease Regulation of the Aged, School of Dentistry, Chosun University, Gwangju, Korea
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  • Jun Lee,

    1. Department of Oral & Maxillofacial Surgery, College of Dentistry, Daejeon Dental Hospital, Wonkwang Bone Regeneration Institute, Wonkwang University, Daejeon, Korea
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  • Seung-Ki Min,

    1. Department of Oral & Maxillofacial Surgery, College of Dentistry, Daejeon Dental Hospital, Wonkwang Bone Regeneration Institute, Wonkwang University, Daejeon, Korea
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  • Yong-Chul Kim,

    1. Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Korea
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  • Sang-Gun Ahn,

    1. Department of Pathology, Research Center for Oral disease Regulation of the Aged, School of Dentistry, Chosun University, Gwangju, Korea
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  • Jung-Hoon Yoon

    1. Department of Oral & Maxillofacial Pathology, College of Dentistry, Daejeon Dental Hospital, Wonkwang Bone Regeneration Institute, Wonkwang University, Daejeon, Korea
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Sang-Gun Ahn, PhD, Department of Pathology, School of Dentistry, Chosun University 375 Dong-Gu, Seoseok-dong, Gwangju, 501-759 Korea. Tel: +82 62 230 6879, Fax: +82 62 223 3205 and Jung-Hoon Yoon, DDS, PhD, Department of Oral & Maxillofacial Pathology, College of Dentistry, Daejeon Dental Hospital, Wonkwang University, Daejeon 302-120, Korea. Tel: +82 42 366 1146, Fax: +82 42 366 1115, E-mails: ahnsg@chosun.ac.kr; opathyoon@wku.ac.kr

Abstract

Background:  Pheophorbide a (Pa) is a chlorine-based photosensitizer derived from an ethnopharmacological herb, and our group recently synthesized Pa by the removal of a magnesium ion and a phytyl group from chlorophyll-a. In this study, the effect of photodynamic therapy (PDT) with synthesized Pa was examined in a human oral squamous cell carcinoma (OSCC) cells.

Methods:  Cells were treated with PDT with Pa, and reactive oxygen species (ROS) and mitochondrial membrane potential [ΔΨ (m)] were examined. Apoptosis was measured using annexin V staining and immunoblot. Autophagy was characterized by the increase in LC3B-II and the formation of autophagosome and acidic vesicular organelles (AVOs).

Results:  Pa-PDT inhibited the proliferation of OSCC cells in a dose-dependent manner. Pa-PDT increased the number of apoptotic cells by inactivating ERK pathway. Pa-PDT also induced autophagy in OSCC cells evidenced by the increased levels of LC3 type II expression and the accumulation of AVOs. The inhibition of autophagy enhanced Pa-PDT-mediated cytotoxicity through an increase in necrosis.

Conclusions:  These results suggest that synthesized Pa-PDT exerts anti-tumor effects by inducing apoptosis and autophagy and provide novel evidence that Pa-PDT induces autophagy, and autophagy inhibition enhances Pa-PDT-mediated necrosis in OSCC cells.

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