2. Academic Validation
  3. E17 exerts anti-tumor activity through inhibiting topo II-mediated chromosomes condensation in CRC cells

E17 exerts anti-tumor activity through inhibiting topo II-mediated chromosomes condensation in CRC cells

  • Biochem Biophys Res Commun. 2019 May 28;513(2):313-318. doi: 10.1016/j.bbrc.2019.04.002.
Ji-Ning Chen 1,  Xing-Kang Wu 2,  Chun-Hua Lu 1,  Xun Li 3
Affiliations

Affiliations

  • 1 Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, 250012, PR China.
  • 2 Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi, 030006, PR China.
  • 3 Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, 250012, PR China. Electronic address: [email protected].
PMID: 30955862 DOI: 10.1016/j.bbrc.2019.04.002
Abstract

Topo II inhibitors, e.g. etoposide, doxorubicin and mitoxantrone, etc., which exert their functions by trapping the covalent 'topo II-DNA cleavable complex' via intercalation into DNA base pairs, leading to DNA damage and degradation of Topo II, and inducing decline of cell sensitivity and corresponding multidrug resistance (MDR). E17 is a recently identified Topo II Inhibitor in our lab which has validated to possess a strong Topo II inhibitory activity on cell viability, colony formation, and cell migration. Especially, E17 can trigger G2/M cell cycle arrest through inhibiting chromosome condensation without causing obvious DNA damage in colorectal Cancer (CRC) HCT116 cell. E17 can also induce the accumulation of topo II-DNA complex without leading to degradation of Topo II, which was different from Topo II inhibitors VP16 or ICRF-187, suggesting E17 might be a potential lead for further development by serving as a strong Topo II Inhibitor.

Keywords

Acridone derivative; Antineoplastic efficacy; E17; Topo II inhibitor.

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