Open AccessPhotodynamic therapy with 5‐aminolaevulinic acid and DNA damage: unravelling roles of p53 and ABCG 2
Author(s) -
Postiglione I.,
Barra F.,
Aloj S. M.,
Palumbo G.
Publication year - 2016
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12274
Subject(s) - comet assay , dna damage , abcg2 , efflux , cell culture , biology , cancer research , photodynamic therapy , cell , cytotoxicity , apoptosis , microbiology and biotechnology , dna , atp binding cassette transporter , chemistry , biochemistry , transporter , in vitro , genetics , gene , organic chemistry
Objectives In spite of high sensitivity of A549 cells (p53 +/+ ) to lethal effects of photodynamic therapy with 5‐aminolaevulinic acid (5‐ ALA / PDT ), DNA damage was observed only in H1299 cells (p53 −/− ), suggesting that p53 may exert a protective effect. Studies on human colon adenocarcinoma cell lines HCT ‐116, and their cognate knockouts for p53, were not entirely consistent with the assumption above. Exploring alternative explanations for such conflicting behaviour, we observed that expression of the ATP ‐binding cassette G2 ( ABCG 2), a regulator of cell component efflux, had important effects on PDT ‐generated DNA injury in PC 3 cells (prostate) which are p53 −/− and positive for ABCG 2. Addition of an ABCG 2 inhibitor in ABCG 2 positive A549 (p53 +/+ ) and PC 3 (p53 −/− ) cells eliminated resistance to DNA damage. Materials and methods All cell lines investigated were incubated with 5‐ ALA and irradiated. Effects of PDT were evaluated assessing residual cell viability, cell‐cycle profiles, Pp IX localization, comet assay and Western blotting. Identical measurements were made in the presence of ABCG 2 inhibitor, in cells expressing the transporter. Results Our data show that cell aptitude to defend its DNA from PDT ‐induced injury was mainly ruled by ABCG 2 expression. These findings, while providing helpful information in predicting effectiveness of 5‐ ALA / PDT , may indicate a way to shift PDT from a palliative to a more effective approach in anti‐cancer therapy.