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

Yu Shih Lin; Yi Chia Shen; Ching Yuan Wu; Ying Ying Tsai; Yao Hsu Yang; Yin Yin Lin; Feng Che Kuan; Cheng Nan Lu; Geng He Chang; Ming Shao Tsai; Cheng Ming Hsu; Reming Albert Yeh; Pei Rung Yang; I. Yun Lee; Li Hsin Shu; Yu Ching Cheng; Hung Te Liu; Yu Huei Wu; Yu Heng Wu; De Ching Chang

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

Yu Shih Lin, Yi Chia Shen, Ching Yuan Wu^*, Ying Ying Tsai, Yao Hsu Yang, Yin Yin Lin, Feng Che Kuan, Cheng Nan Lu, Geng He Chang, Ming Shao Tsai, Cheng Ming Hsu, Reming Albert Yeh, Pei Rung Yang, I. Yun Lee, Li Hsin Shu, Yu Ching Cheng, Hung Te Liu, Yu Huei Wu, Yu Heng Wu, De Ching Chang

^*Corresponding author for this work

School of Traditional Chinese Medicine

Research output: Contribution to journal › Journal Article › peer-review

84 Scopus citations

Abstract

Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is 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.

Original language	English
Article number	1226
Journal	Frontiers in Pharmacology
Volume	10
Issue number	OCT
DOIs	https://doi.org/10.3389/fphar.2019.01226
State	Published - 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 Lin, Shen, Wu, 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.

Keywords

Breast carcinoma
Danshen
Dihydroisotanshinone I
Ferroptosis
GPX4
National Health Insurance Research Database

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10.3389/fphar.2019.01226

Cite this

Lin, Y. S., Shen, Y. C., Wu, C. Y., Tsai, Y. Y., Yang, Y. H., Lin, Y. Y., Kuan, F. C., Lu, C. N., Chang, G. H., Tsai, M. S., Hsu, C. M., Yeh, R. A., Yang, P. R., Lee, I. Y., Shu, L. H., Cheng, Y. C., Liu, H. T., Wu, Y. H., Wu, Y. H., & Chang, D. C. (2019). Danshen improves survival of patients with breast cancer and dihydroisotanshinone I induces ferroptosis and apoptosis of breast cancer cells. Frontiers in Pharmacology, 10(OCT), Article 1226. https://doi.org/10.3389/fphar.2019.01226

@article{88b659285237436681b3baa946dcba50,

title = "Danshen improves survival of patients with breast cancer and dihydroisotanshinone I induces ferroptosis and apoptosis of breast cancer cells",

abstract = "Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is 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 = "Breast carcinoma, Danshen, Dihydroisotanshinone I, Ferroptosis, GPX4, National Health Insurance Research Database",

author = "Lin, {Yu Shih} and Shen, {Yi Chia} and Wu, {Ching Yuan} and Tsai, {Ying Ying} and Yang, {Yao Hsu} and Lin, {Yin Yin} and Kuan, {Feng Che} and Lu, {Cheng Nan} and Chang, {Geng He} and Tsai, {Ming Shao} and Hsu, {Cheng Ming} and Yeh, {Reming Albert} and Yang, {Pei Rung} and Lee, {I. Yun} and Shu, {Li Hsin} and Cheng, {Yu Ching} and Liu, {Hung Te} and Wu, {Yu Huei} and Wu, {Yu Heng} and Chang, {De Ching}",

note = "Publisher Copyright: Copyright {\textcopyright} 2019 Lin, Shen, Wu, 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.",

year = "2019",

doi = "10.3389/fphar.2019.01226",

language = "英语",

volume = "10",

journal = "Frontiers in Pharmacology",

issn = "1663-9812",

number = "OCT",

}

Lin, YS, Shen, YC, Wu, CY, Tsai, YY, Yang, YH, Lin, YY, Kuan, FC, Lu, CN, Chang, GH, Tsai, MS, Hsu, CM, Yeh, RA, Yang, PR, Lee, IY, Shu, LH, Cheng, YC, Liu, HT, Wu, YH, Wu, YH & Chang, DC 2019, 'Danshen improves survival of patients with breast cancer and dihydroisotanshinone I induces ferroptosis and apoptosis of breast cancer cells', Frontiers in Pharmacology, vol. 10, no. OCT, 1226. https://doi.org/10.3389/fphar.2019.01226

TY - JOUR

T1 - Danshen improves survival of patients with breast cancer and dihydroisotanshinone I induces ferroptosis and apoptosis of breast cancer cells

AU - Lin, Yu Shih

AU - Shen, Yi Chia

AU - Wu, Ching Yuan

AU - Tsai, Ying Ying

AU - Yang, Yao Hsu

AU - Lin, Yin Yin

AU - Kuan, Feng Che

AU - Lu, Cheng Nan

AU - Chang, Geng He

AU - Tsai, Ming Shao

AU - Hsu, Cheng Ming

AU - Yeh, Reming Albert

AU - Yang, Pei Rung

AU - Lee, I. Yun

AU - Shu, Li Hsin

AU - Cheng, Yu Ching

AU - Liu, Hung Te

AU - Wu, Yu Huei

AU - Wu, Yu Heng

AU - Chang, De Ching

N1 - Publisher Copyright: Copyright © 2019 Lin, Shen, Wu, 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.

PY - 2019

Y1 - 2019

N2 - Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is 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.

AB - Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is 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.

KW - Breast carcinoma

KW - Danshen

KW - Dihydroisotanshinone I

KW - Ferroptosis

KW - GPX4

KW - National Health Insurance Research Database

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U2 - 10.3389/fphar.2019.01226

DO - 10.3389/fphar.2019.01226

M3 - 文章

AN - SCOPUS:85074844975

SN - 1663-9812

VL - 10

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

IS - OCT

M1 - 1226

ER -

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

Abstract

Bibliographical note

Keywords

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