Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway

Yu Shih Lin, Yin Yin Lin, Yao Hsu Yang, Chun Liang 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, Kuan Der Lee, De Ching Chang, Ching Yuan Wu

Research output: Contribution to journalArticle

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Abstract

Background: Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer. Methods: Antrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western's blotting assay. Results: Our results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10-6M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells. Conclusions: These results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.

Original languageEnglish
Article number152
JournalBMC Complementary and Alternative Medicine
Volume18
Issue number1
DOIs
Publication statusPublished - May 9 2018

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Antrodia
S-Phase Kinase-Associated Proteins
Tamoxifen
MicroRNAs
Apoptosis
Breast Neoplasms
MCF-7 Cells
Ethanol
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Agaricales
Taiwan
Estrogen Receptors
Antineoplastic Agents
Neoplasms
Flow Cytometry

Keywords

  • Antrodia cinnamomea
  • Breast cancer
  • MicroRNA
  • Skp2
  • Tamoxifen-resistant

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway. / Lin, Yu Shih; Lin, Yin Yin; Yang, Yao Hsu; Lin, Chun Liang; Kuan, Feng Che; Lu, Cheng Nan; Chang, Geng He; Tsai, Ming Shao; Hsu, Cheng Ming; Yeh, Reming Albert; Yang, Pei Rung; Lee, I. Yun; Shu, Li Hsin; Cheng, Yu Ching; Liu, Hung Te; Lee, Kuan Der; Chang, De Ching; Wu, Ching Yuan.

In: BMC Complementary and Alternative Medicine, Vol. 18, No. 1, 152, 09.05.2018.

Research output: Contribution to journalArticle

Lin, YS, Lin, YY, Yang, YH, Lin, CL, Kuan, FC, Lu, CN, Chang, GH, Tsai, MS, Hsu, CM, Yeh, RA, Yang, PR, Lee, IY, Shu, LH, Cheng, YC, Liu, HT, Lee, KD, Chang, DC & Wu, CY 2018, 'Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway', BMC Complementary and Alternative Medicine, vol. 18, no. 1, 152. https://doi.org/10.1186/s12906-018-2204-y
Lin, Yu Shih ; Lin, Yin Yin ; Yang, Yao Hsu ; Lin, Chun Liang ; Kuan, Feng Che ; Lu, Cheng Nan ; Chang, Geng He ; Tsai, Ming Shao ; Hsu, Cheng Ming ; Yeh, Reming Albert ; Yang, Pei Rung ; Lee, I. Yun ; Shu, Li Hsin ; Cheng, Yu Ching ; Liu, Hung Te ; Lee, Kuan Der ; Chang, De Ching ; Wu, Ching Yuan. / Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway. In: BMC Complementary and Alternative Medicine. 2018 ; Vol. 18, No. 1.
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abstract = "Background: Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer. Methods: Antrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western's blotting assay. Results: Our results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10-6M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells. Conclusions: These results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.",
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AU - Lin, Yu Shih

AU - Lin, Yin Yin

AU - Yang, Yao Hsu

AU - Lin, Chun Liang

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 - Lee, Kuan Der

AU - Chang, De Ching

AU - Wu, Ching Yuan

PY - 2018/5/9

Y1 - 2018/5/9

N2 - Background: Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer. Methods: Antrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western's blotting assay. Results: Our results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10-6M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells. Conclusions: These results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.

AB - Background: Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer. Methods: Antrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western's blotting assay. Results: Our results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10-6M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells. Conclusions: These results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.

KW - Antrodia cinnamomea

KW - Breast cancer

KW - MicroRNA

KW - Skp2

KW - Tamoxifen-resistant

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