Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Cremastranone-Derived Homoisoflavanes Suppress the Growth of Breast Cancer Cells via Cell Cycle Arrest and Caspase-Independent Cell Death

  • Yeram Choi (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Sangkyu Park (Biotechnology Research Institute, Chungbuk National University) ;
  • Seul Lee (College of Pharmacy, Gachon University) ;
  • Ha-Eun Shin (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Sangil Kwon (College of Pharmacy, Gachon University) ;
  • Jun-Kyu Choi (Biotechnology Research Institute, Chungbuk National University) ;
  • Myeong-Heon Lee (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Seung-Yong Seo (College of Pharmacy, Gachon University) ;
  • Younghee Lee (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
  • Received : 2023.03.14
  • Accepted : 2023.04.19
  • Published : 2023.09.01
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Abstract

Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.

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).

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