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Front. Pharmacol. | doi: 10.3389/fphar.2019.01226

Danshen improves survival of patients with breast cancer and dihydroisotanshinone I induces ferroptosis and apoptosis of breast cancer cells

 Ching-Yuan Wu1*, Yu-Shih Lin1, Yi-Chia Shen1, Ying-Ying Tsai1, Yao-Hsu Yang1, Yin-Yin Lin1, Feng-Che Kuan1, Cheng-Nan Lu2, Geng-He Chang1, Ming-Shao Tsai1, Cheng-Ming Hsu1, Reming-Albert Yeh1, Pei-Rung Yang1, I-Yun Lee1, Li-Hsin Shu1, Yu-Ching Cheng1, Hung-Te Liu1, Yu-Huei Wu1, Yu-Heng Wu1 and De-Ching Chang3
  • 1Chiayi Chang Gung Memorial Hospital, Taiwan
  • 2Kaohsiung Chang Gung Memorial Hospital, Taiwan
  • 3National Chung Cheng University, Taiwan

Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it’s definite clinical effort and mechanism on breast cancer is unclear. In our study, we used the real-world database to investigate in vivo protective effort of danshen in the breast cancer patients through using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). In vitro, human breast cancer cells (MCF-7 cells and MDA-MB-231 cells) were used to investigate the effect and the underlying mechanism through XTT assay, flow cytometry, glutathione peroxidase (GPX) activity assay, GSH (reduced glutathione)/GSSG (oxidized glutathione), malondialdehyde (MDA) and western blot analysis. The in vivo effect was investigated through a xenograft nude mouse model. We found that dihydroisotanshinone I (DT), a pure compound present in danshen, can inhibit the growth of breast carcinoma cells, including MCF-7 cells and MDA-MB-231 cells. Moreover, DT induced apoptosis and ferroptosis in these breast cancer cells. DT also repressed the protein expression of GPX4 (Glutathione peroxidase 4). For in vivo study, DT treatment also significantly inhibited the final tumor volume without adverse effects in a xenograft nude mouse model. In conclusion, Danshen has protective efforts in breast cancer patients, which could be attributed to DT through inducing apoptosis and ferroptosis of breast cancer cells.

Keywords: dihydroisotanshinone I, breast carcinoma, GPx4, National Health Insurance Research Database, Danshen, ferroptosis

Received: 18 Apr 2019; Accepted: 23 Sep 2019.

Copyright: © 2019 Wu, Lin, Shen, Tsai, Yang, Lin, Kuan, Lu, Chang, Tsai, Hsu, Yeh, Yang, Lee, Shu, Cheng, Liu, Wu, Wu and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Ching-Yuan Wu, Chiayi Chang Gung Memorial Hospital, Chiayi City, Taiwan, smbepigwu77@gmail.com