{
  "abstract": "Sesamol (3,4-methylenedioxyphenol) is a unique natural phenolic compound derived from sesame seeds that is characterized by its concurrent phenolic and methylenedioxy moieties. The purpose of this study was to investigate the tyrosinase-mediated metabolic activation of sesamol to determine whether a cytotoxic quinone intermediate is produced, mirroring the mechanism established for p-substituted phenols such as resveratrol. Although sesamol is recognized as a potent tyrosinase inhibitor, we demonstrate that in the presence of catalytic amounts of L-DOPA, it serves as an efficient substrate for tyrosinase-mediated bioactivation. The resulting metabolite, sesamol-5,6-quinone, was identified via reduction with NaBH₄ or ascorbic acid to its corresponding catechol, followed by isolation through acetylation to stabilize the transient species. The reactive nature of sesamol-5,6-quinone was confirmed through the formation of covalent adducts with N-acetylcysteine. In metabolic experiments using human tyrosinase-expressing 293T cells, we identified the reactive metabolite, sesamol-5,6-quinone, through the formation of intracellular thiol adducts released into the medium. While sesamol is systemically protective, it induced a marked tyrosinase-dependent cytotoxicity in B16BL6 melanoma cells, which was significantly suppressed by tyrosinase knockdown. Crucially, sesamol oligomers exhibited potent pro-oxidant activity, generating hydrogen peroxide and depleting reduced glutathione through its oxidation to GSSG. These findings suggest that tyrosinase-mediated conversion transforms sesamol into a highly reactive pro-oxidant, which induces substantial cytotoxicity in melanin-producing cells via protein arylation and profound redox imbalance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Technology, School of Health Sciences, Gifu University of Medical Science, 795-1 Nagamine, Ichihiraga, Seki 501-3892, Gifu, Japan.",
    "Institute for Melanin Chemistry, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Aichi, Japan.",
    "Division of Biochemistry, National Institute of Health Sciences, Kawasaki-ku, Kawasaki 210-9501, Kanagawa, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hitomi Tanaka",
      "orcid": "0000-0002-5646-9620"
    },
    {
      "affs": [
        2
      ],
      "name": "Tomoko Nishimaki-Mogami",
      "orcid": "0000-0003-0194-2377"
    },
    {
      "affs": [
        1
      ],
      "name": "Shosuke Ito",
      "orcid": "0000-0001-9182-5144"
    },
    {
      "affs": [
        1
      ],
      "name": "Kazumasa Wakamatsu",
      "orcid": "0000-0003-1748-9001"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4117c0q5hb6jn.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198597",
  "fulltext_url": "https://europepmc.org/articles/PMC13665154",
  "id": "4117c0q5hb6jn",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://europepmc.org/article/MED/42883844",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "3005|Bioactive Compounds and Antitumor Agents"
    ]
  ],
  "openalex": "W7214310443",
  "pdf_url": "https://europepmc.org/articles/PMC13665154?pdf=render",
  "pmcid": "PMC13665154",
  "pmid": "42883844",
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4117c0q5hb6jn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42883844",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883844"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3005|Bioactive Compounds and Antitumor Agents",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "The Dual Nature of Sesamol: Tyrosinase-Dependent Bioactivation from an Inhibitor to a Cytotoxic Pro-Oxidant.",
  "title_text": "The Dual Nature of Sesamol: Tyrosinase-Dependent Bioactivation from an Inhibitor to a Cytotoxic Pro-Oxidant.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/4117c0q5hb6jn",
  "venue": "International journal of molecular sciences",
  "versions": []
}