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KMID : 0606920230310050526
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Biomolecules & Therapeutics
2023 Volume.31 No. 5 p.526 ~ p.535
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Cremastranone-Derived Homoisoflavanes Suppress the Growth of Breast Cancer Cells via Cell Cycle Arrest and Caspase-Independent Cell Death
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Choi Ye-Ram
Park Sang-Kyu
Lee Seul
Shin Ha-Eun
Kwon Sang-Il
Choi Jun-Kyu
Lee Myeong-Heon
Seo Seung-Yong
Lee Young-Hee
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Abstract
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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.
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KEYWORD
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Breast cancer, Cremastranone, Homoisoflavane, Cell cycle arrest, Caspase-independent cell death, Anti-cancer
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