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Ascorbate anti‐cancer activity is increased by Mn(III) N ‐alkylpyridylporphyrins through production of reactive oxygen species
Author(s) -
Bader Bader Hassan,
Tovmayasan Artak,
Craik James,
Benov Ludmil,
Batinic Haberle Ines
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1107.7
Subject(s) - reactive oxygen species , chemistry , cancer cell , redox , flow cytometry , mtt assay , superoxide dismutase , cytotoxicity , viability assay , cell growth , biochemistry , cytotoxic t cell , apoptosis , cancer , oxidative stress , microbiology and biotechnology , biology , in vitro , organic chemistry , genetics
Ascorbate (Asc) has shown potential for cancer therapy, and cancer cells typically accumulate porphyrins and display aberrant redox homeostasis. Mn(III) N ‐alkylpyridylporphyrins (MnPs) are redox‐active superoxide dismutase mimetics with many prospective therapeutic applications. This study examined how structural modifications of MnPs might affect their anticancer activity through selective cellular targeting of production of reactive oxygen species (ROS) produced by redox‐cycling with ascorbate. Methods PII/MDA ER‐negative human breast cancer and non‐tumorigenic HBL100 human breast epithelial cell lines were used as model systems. Uptake of MnPs and ascorbate oxidation rates were determined spectrophotometrically. MTT/SRB assays were used to investigate cytotoxic and anti‐proliferative actions of MnPs and Asc, and combinations thereof. Membrane damage and cell death mechanisms were investigated by flow cytometry. Results Ascorbate and MnPs redox‐cycle to generate cytotoxic ROS, mainly H 2 O 2 . Anticancer efficiency of MnPs correlated with ability to oxidize ascorbate; differences in cellular uptake and subcellular distribution had only minor effect. Conclusions The major factor determining MnPs’ anticancer activity in cell culture models is redox potential Support or Funding Information Support: College of Graduate Studies, Kuwait University and Research Sector, Kuwait University; Research Grant YM04/14 and University Grant SRUL02/13