Antitumor activity of a novel Aurora A/B kinases inhibitor TY-011 against gastric cancer by inducing DNA damage

  • Anticancer Drugs. 2020 Jun;31(5):440-451. doi: 10.1097/CAD.0000000000000928.
Tongtong Jiang  1 ,  Wang Liu  1 ,  Yu Lu  2 ,  Yanfen Fang  1 ,  Rui Chen  1 ,  Wanli Zhang  1 ,  Xuan Liu  3 ,  Xiongwen Zhang  1
Affiliations
  • 1. Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai.
  • 2. Department of Project Management, Nanjing Tianyi Bioscience Co. Ltd, Nanjing.
  • 3. Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PMID: 32187025 DOI: 10.1097/CAD.0000000000000928
Abstract

TY-011, a novel Aurora A/B kinases inhibitor, was found in our previous study to exhibit prominent inhibitory effects on growth of gastric Cancer, both in vitro and in vivo. To clarify the mechanisms of TY-011 in inhibiting proliferation of gastric Cancer cells, the effects of TY-011 on Mitosis, cell cycle, Apoptosis and cellular DNA were checked in the present study. Our results showed that TY-011 treatment induced aberrant Mitosis, G2/M phase arrest and Apoptosis. Importantly, TY-011 induced evident DNA damage in MGC-803 and MKN-45 human gastric Cancer cells, which was further characterized as DNA double-strand break. Furthermore, cells treated with TY-011 appeared to generate multiple spindle fibers emanating from several spindle poles, leading to poly-merotelic kinetochore. These results suggested that TY-011 induced abnormal microtubule-kinetochores attachment and thus DNA damage, Apoptosis and finally inhibition of cell proliferation of human gastric Cancer cells.

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