2. Academic Validation
  3. The fungal natural product (1S,3S)-austrocortirubin induces DNA damage in HCT116 cells via a mechanism unique from other DNA damaging agents

The fungal natural product (1S,3S)-austrocortirubin induces DNA damage in HCT116 cells via a mechanism unique from other DNA damaging agents

  • Bioorg Med Chem Lett. 2015 Jan 15;25(2):249-53. doi: 10.1016/j.bmcl.2014.11.055.
Yao Wang 1,  Md Amirul Islam 1,  Rohan A Davis 2,  Shelli R McAlpine 3
Affiliations

Affiliations

  • 1 Department of Chemistry, University of New South Wales, Kensington, NSW 2052, Australia.
  • 2 Eskitis Institute, Griffith University, Brisbane, QLD 4006, Australia.
  • 3 Department of Chemistry, University of New South Wales, Kensington, NSW 2052, Australia. Electronic address: s.mcalpine@unsw.edu.au.
PMID: 25499433 DOI: 10.1016/j.bmcl.2014.11.055
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.

Keywords

(1S,3S)-Austrocortirubin; Anticancer; DNA damage; DNA intercalators; Doxorubicin; HCT116; Tetrahydroanthraquinone.

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