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Planta Med 2019; 85(16): 1275-1286
DOI: 10.1055/a-1013-1439
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Yuanhuatine from Daphne genkwa selectively induces mitochondrial apoptosis in estrogen receptor α-positive breast cancer cells in vitro

Ying-Ying Zhang
1   School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Peopleʼs Republic of China;
,
Xin-Yue Shang
1   School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Peopleʼs Republic of China;
,
Xue-Wen Hou
1   School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Peopleʼs Republic of China;
,
Ling-Zhi Li
1   School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Peopleʼs Republic of China;
,
Wei Wang
1   School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Peopleʼs Republic of China;
,
Toshihiko Hayashi
2   China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China
3   Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, Tokyo, Japan
,
Yan Zhang
1   School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Peopleʼs Republic of China;
,
Guo-Dong Yao
1   School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Peopleʼs Republic of China;
,
Shao-Jiang Song
1   School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Peopleʼs Republic of China;
› Author Affiliations
Further Information

Publication History

received 24 April 2019
revised 14 August 2019

accepted 12 September 2019

Publication Date:
18 October 2019 (online)

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Abstract

Breast cancer is one of the most common cancers diagnosed among women worldwide. Estrogen receptor alpha (ERα) is a transcriptional factor that plays an important role in the development and progression of breast cancer. Yuanhuatine, a natural daphnane-type diterpenoid extracted from Daphne genkwa, was reported to exhibit significant cytotoxicity against breast cancer cells. However, the underlying mechanism is still unclear. In this study, we evaluated the cytotoxicity of yuanhuatine on two breast cancer cell lines that are ERα-positive and -negative. The results show that yuanhuatine inhibits the growth of ERα-positive cells (MCF-7) with much stronger inhibitory activity (IC50 = 0.62 µM) compared with positive control tamoxifen (IC50 = 14.43 µM). However, no obvious cytotoxicity was observed in ERα-negative cells (MDA-MB-231). Subsequent experiment also indicated that yuanhuatine markedly induced mitochondrial dysfunction, leading to apoptosis in MCF-7 cells. Molecular docking studies suggest the potential interactions between yuanhuatine and ERα. Immunofluorescence staining and Western blot analysis indicated that yuanhuatine down-regulated the expression of ERα in MCF-7 cells. MPP, a specific ERα inhibitor, significantly enhanced yuanhuatine-induced mitochondrial dysfunction and apoptosis in MCF-7 cells. On the contrary, the treatment with yuanhuatine causes no apoptosis in MM231 cells. Altogether, in vitro and in silico results suggested that ERα down-regulation was involved in yuanhuatine-induced mitochondrial dysfunction and apoptosis in ERα-positive breast cancer cells. Thus, yuanhuatine could be a potential candidate for treating ERα-positive breast cancer.

Key words

Daphne genkwa - Thymelaeaceae - breast cancer - estrogen receptor α - apoptosis

Supporting Information

    Additional information about the induction of cells apoptosis by yuanhuatine treatment of MM231 cells and the pharmacokinetic properties of yuanhuatine predicted by PreADMET web server are available in Supporting Information section.

  • Supporting Information
 

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