Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Synthetic Homoisoflavane Derivatives of Cremastranone Suppress Growth of Colorectal Cancer Cells through Cell Cycle Arrest and Induction of Apoptosis

  • Shin, Ha-Eun (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Lee, Seul (College of Pharmacy, Gachon University) ;
  • Choi, Yeram (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Park, Sangkyu (Biotechnology Research Institute, Chungbuk National University) ;
  • Kwon, Sangil (College of Pharmacy, Gachon University) ;
  • Choi, Jun-Kyu (Biotechnology Research Institute, Chungbuk National University) ;
  • Seo, Seung-Yong (College of Pharmacy, Gachon University) ;
  • Lee, Younghee (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
  • Received : 2022.07.01
  • Accepted : 2022.07.20
  • Published : 2022.11.01
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Abstract

Colorectal cancer is diagnosed as the third most prevalent cancer; thus, effective therapeutic agents are urgently required. In this study, we synthesized six homoisoflavane derivatives of cremastranone and investigated their cytotoxic effects on the human colorectal cancer cell lines HCT116 and LoVo. We further examined the related mechanisms of action using two of the potent compounds, SH-19027 and SHA-035. They substantially reduced the cell viability and proliferation in a dose-dependent manner. Treatment with SH-19027 and SHA-035 induced cell cycle arrest at the G2/M phase and increased expression of p21 both of which are implicated in cell cycle control. In addition, the apoptotic cell population and apoptosis-associated marker expression were accordingly increased. These results suggest that the synthesized cremastranone derivatives have anticancer effects through the suppression of cell proliferation and induction of apoptosis. Therefore, the synthesized cremastranone derivatives could be applied as novel therapeutic agents against colorectal cancer.

Keywords

Acknowledgement

This work was supported by grants from the National Research Foundation funded by the Korean government, Ministry of Science, ICT, and Future Planning (NRF-2020R1I1A1A01072992, NRF-2021R1A2C1006767), and the Gachon University research fund of 2019 (GCU-2019-0306).

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