Anticancer Properties of a New Hybrid Analog AD-013 Combining a Coumarin Scaffold with an α-methylene-δ-lactone Motif

Author(s): Angelika Dlugosz, Katarzyna Gach-Janczak, Jacek Szymanski, Dariusz Deredas, Henryk Krawczyk, Tomasz Janecki, Anna Janecka*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 18 , Issue 3 , 2018

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Graphical Abstract:


Background: Coumarin is a natural phytochemical but as such has no medical uses. However, various natural and synthetic coumarin analogs attract attention due to their interesting biological properties.

Objective: Here, we evaluated and compared anticancer properties of a new synthetic hybrid compound AD- 013, which integrates a coumarin moiety and an α-methylene-δ-lactone motif, with novobiocin, a natural antibiotic bearing a coumarin scaffold.

Methods: Cytotoxic activities of compound AD-013 and novobiocin were assessed by the MTT assay. In order to explore the mechanism of anticancer activity of analog AD-013, we performed quantitative real-time PCR analysis of apoptosis- and cell cycle-related genes. The ability of AD-013 and novobiocin to induce apoptosis and DNA damage was studied by flow cytometry.

Results: The cytotoxic activity of this new compound was compared with the activity of a coumarin-based antibiotic novobiocin against two cancer cell lines, MCF-7 and HL-60 and also against normal human cells, MCF- 10A and HUVEC. AD-013 was much more cytotoxic than novobiocin in both cancer cell lines and showed some selectivity against MCF-7 cancer cells as compared with MCF-10A healthy cells. Expression levels of the pro-apoptotic genes significantly increased while the anti-apoptotic genes, were down-regulated for both compounds in both cancer cell lines.

AD-013 was able to inhibit cell proliferation, generate DNA damage and induce apoptosis. The obtained data showed that this compound caused the cell cycle arrest in subG0/G1 in both cancer cell lines.

Conclusion: The new hybrid analog was a much stronger apoptosis inducer than novobiocin and activated the intrinsic pathway of apoptosis.

Keywords: Hybrid molecules, MTT test, apoptosis, cell cycle, real-time PCR, flow cytometry.

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Article Details

Year: 2018
Published on: 04 June, 2018
Page: [450 - 457]
Pages: 8
DOI: 10.2174/1871520617666170921123654
Price: $65

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