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α-Pyrone Derivatives from a Streptomyces Strain Resensitize Tamoxifen Resistance in Breast Cancer Cells |
Rui-Min Yang1,2, Xiu-Lei Zhang1, Li Wang1, Jian-Ping Huang1, Jing Yang1, Yi-Jun Yan1, Jian-Ying Luo1, Xiang-Ting Wang1, Sheng-Xiong Huang1 |
1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; 2. University of the Chinese Academy of Sciences, Beijing 100049, People's Republic of China |
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Abstract Tamoxifen resistance (TamR) is the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen. In order to look for noncytotoxic natural products with the ability to reverse TamR, an extract from strain Streptomyces sp. KIB-H0495 was detected to be active. Subsequent large scale fermentation and isolation led to the isolation of four α-pyrone derivatives including two new compounds, violapyrones J (2) and K (3), and two known analogues, violapyrones B (1) and I (4). Further bioactivity assays indicated that only 1 and 3 exerted potent resensitization effects on MCF-7/TamR cells at a concentration of 1 μM. Owing to the simple structures of 1 and 3, these two compounds might have potential for further investigation as novel tamoxifen resensitization agent in breast cancer chemotherapy.
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Keywords
Breast cancer
Tamoxifen resistance
Resensitization
α-Pyrone derivatives
Streptomyces
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Fund:This research was financially supported by the National Natural Science Foundation of China to S-X.H (No. 81522044) and to X.W (No. 31471226), High-end Science and Technology Talents Program of Yunnan Province to S-X.H (No. 2013HA022), and a Grant from the Thousand Youth Talents Program of China. |
Issue Date: 07 February 2018
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