title: The fungal natural product (1S,3S)-austrocortirubin induces DNA damage in HCT116 cells via a mechanism unique from other DNA damaging agents.
abstract: Screening a series of natural product-based tetrahydroanthraquinones led to the identification of a novel molecule, (1S,3S)-austrocortirubin (2), which acts via inducing DNA damage. Compound 2 has a GI50 of 3μM against HCT116 and induces apoptosis. Mechanism of action studies indicate that it causes significant DNA damage during G0/G1, S, and G2 cell cycle phases. Cells are stopped at the G2/M phase checkpoint, and do not reach mitosis due to large amounts of DNA damage. Thus, compound 2 exhibits a unique mechanism of action, one that is distinct from doxorubicin, despite the high degree of structural homology between these two quinone-based structures.
authors.affiliation: Department of Chemistry, University of New South Wales, Kensington, NSW 2052, Australia.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of New South Wales, Kensington, NSW 2052, Australia.
authors.forename: Md Amirul
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Eskitis Institute, Griffith University, Brisbane, QLD 4006, Australia.
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Davis
authors.affiliation: Department of Chemistry, University of New South Wales, Kensington, NSW 2052, Australia. Electronic address: s.mcalpine@unsw.edu.au.
authors.forename: Shelli R
authors.initials: SR
authors.lastname: McAlpine
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D006801:Humans
chemical_list: D000880:Anthraquinones; D001688:Biological Products; C419350:austrocortirubin
keywords: (1S,3S)-Austrocortirubin; Anticancer; DNA damage; DNA intercalators; Doxorubicin; HCT116; Tetrahydroanthraquinone