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Etretinate enhances the susceptibility of human skin squamous cell carcinoma cells to 5‐aminolaevulic acid‐based photodynamic therapy
Author(s) -
Ishida N.,
Watanabe D.,
Akita Y.,
Nakano A.,
Yamashita N.,
Kuhara T.,
Yanagishita T.,
Takeo T.,
Tamada Y.,
Matsumoto Y.
Publication year - 2009
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/j.1365-2230.2008.03003.x
Subject(s) - etretinate , photodynamic therapy , propidium iodide , cytotoxicity , protoporphyrin ix , cytotoxic t cell , apoptosis , cancer research , intracellular , annexin , cell culture , chemistry , cancer cell , pharmacology , in vitro , microbiology and biotechnology , cancer , biochemistry , medicine , immunology , biology , programmed cell death , psoriasis , genetics , organic chemistry
Summary Background. Photodynamic therapy (PDT) with 5‐aminolaevulinic acid (5‐ALA) is a noninvasive and effective treatment for superficial skin cancers. Etretinate, a derivate of vitamin A, with the chemical formula ethyl(2E,4E,6E,8E)‐9‐(4‐methoxy‐2,3,6‐trimethylphenyl)‐3,7‐dimethyl‐2,4,6,8‐nona‐tetraenoate, has been reported to have antitumour effects and to regulate the proliferation and differentiation of skin cancers. Objective. In order to develop more efficient PDT, we investigated whether etretinate enhanced the cytotoxic action of ALA‐based PDT against human squamous cell carcinoma cell line, HSC‐5. Method. The in vitro cytotoxicity was measured using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Apoptotic cells were detected by double‐staining with fluorescent annexin V and propidium iodide. Intracellular protoporphyrin IX (PpIX) converted from exogenous ALA was measured by a fluorescence meter. Results. HSC‐5 cells pretreated with a nontoxic concentration of etretinate became more susceptible to the cytotoxic action of ALA‐based PDT. Etretinate‐pretreated cells underwent apoptosis in response to ALA‐based PDT. Etretinate pretreatment resulted in enhanced accumulation of ALA‐dependent intracellular PpIX. Conclusions. The results suggest that etretinate enhances the susceptibility of HSC‐5 cells to ALA‐based PDT via the intracellular increase of ALA‐dependent PpIX. Etretinate might be useful for improvement of ALA‐based PDT.