Metformin enhances the cytotoxicity of 5-aminolevulinic acid-mediated photodynamic therapy in vitro

The biguanide metformin is a drug widely used for the treatment of type 2 diabetes. Metformin enhances the cytotoxicity of chemotherapy by promoting the adenosine monophosphate-activated protein kinase (AMPK) autophagy signaling pathway. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA),...

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Published in:Oncology letters 2017-07, Vol.14 (1), p.1049-1053
Main Authors: Osaki, Tomohiro, Yokoe, Inoru, Takahashi, Kiwamu, Inoue, Katsushi, Ishizuka, Masahiro, Tanaka, Tohru, Azuma, Kazuo, Murahata, Yusuke, Tsuka, Takeshi, Itoh, Norihiko, Imagawa, Tomohiro, Okamoto, Yoshiharu
Format: Article
Language:English
Subjects:
Antidiabetics
Apoptosis
Autophagy
Cancer therapies
Cell culture
Chemotherapy
Cytotoxicity
Gangrene
Kinases
Lung cancer
Morphology
Photodynamic therapy
Proteins
Studies
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Summary:The biguanide metformin is a drug widely used for the treatment of type 2 diabetes. Metformin enhances the cytotoxicity of chemotherapy by promoting the adenosine monophosphate-activated protein kinase (AMPK) autophagy signaling pathway. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), leads to apoptosis when PpIX accumulates in the mitochondria, and also leads to autophagy through activation of AMPK. In the present study, the effect of metformin in combination with 5-ALA-PDT was evaluated in KLN205 lung cancer cells. At a fluence of 5 J/cm , 5-ALA-PDT in combination with 5 mM metformin exhibited significantly increased cytotoxicity compared with that observed with 0 and 0.1 mM metformin (P=0.0197 and P=0.0423, respectively). The cells treated with 5-ALA-PDT and metformin exhibited condensation of nuclear chromatin and the presence of autophagosomes. These results indicate that apoptosis and autophagy occur in KLN205 cells following combined treatment with 5-ALA-PDT and metformin. The results from the present study are the first to indicate, to the best of our knowledge, that metformin potentiates the efficacy of 5-ALA-PDT.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2017.6237