title: Photodynamic therapy with 5-aminolaevulinic acid and DNA damage: unravelling roles of p53 and ABCG2.
abstract: OBJECTIVE
  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 (ABCG2), a regulator of cell component efflux, had important effects on PDT-generated DNA injury in PC3 cells (prostate) which are p53(-/-) and positive for ABCG2. Addition of an ABCG2 inhibitor in ABCG2 positive A549 (p53(+/+) ) and PC3 (p53(-/-) ) cells eliminated resistance to DNA damage.
  
  
  METHODS
  All cell lines investigated were incubated with 5-ALA and irradiated. Effects of PDT were evaluated assessing residual cell viability, cell-cycle profiles, PpIX localization, comet assay and Western blotting. Identical measurements were made in the presence of ABCG2 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 ABCG2 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.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Postiglione
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Barra
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: S M
authors.initials: SM
authors.lastname: Aloj
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: G
authors.identifier: http://orcid.org/0000-0001-9380-8436
authors.initials: G
authors.lastname: Palumbo
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism*; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012007:Rectum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D009363:Neoplasm Proteins; D017319:Photosensitizing Agents; D016159:Tumor Suppressor Protein p53; D000622:Aminolevulinic Acid