Antrodia cinnamomea sensitizes radio-/chemo-therapy of cancer stem-like cells by modulating microRNA expression

Yu Kai Su, Ping Hsiao Shih, Wei Hwa Lee, Oluwaseun Adebayo Bamodu, Alexander T.H. Wu, Chun Chih Huang, Yew Min Tzeng, Michael Hsiao, Chi Tai Yeh, Chien Min Lin

Research output: Contribution to journalArticle

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Abstract

Ethnopharmacological relevance The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention. However, the anti-CSC capability of A. Cinnamomea is not clear yet. Aim of the study To investigate the inhibitory effect of A. cinnamomea mycelium and extract on CSCs derived from various human cancer cell lines using our in-house therapeutics and human genome-wide miRNA screening panels. Materials and methods A broad range of human cancer cell lines, including the acute monocytic leukemia (THP-1), glioblastoma multiforme (GBM 8401), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), hepatoblastoma (HepG2), colorectal adenocarcinoma (SW620), and foreskin fibroblast (HS68), were exposed to A. cinnamomea in this study. CD133+ CSCs generated from the cell lines were characterized and isolated by flow cytometry, effect of chemo- and radiotherapy was assessed using the MTT assay, while the RT-PCR and human genome wide qRT-PCR determined the differential gene expression patterns. A comparative analysis of the anticancer effect of A. cinnamomea and Cisplatin, Taxol, or irradiation was also performed. Results Our results indicated that A. cinnamomea mycelium and its ethyl acetate extracts showed anti-proliferation effects against all types of CSCs, especially the lung, breast, and head and neck squamous cell carcinoma CSCs. Furthermore, CSCs treatment with A. cinnamomea combined with irradiation or chemotherapeutics demonstrated significant anti-cancer effect. We also established an association between the CSC-inhibitory effect of A. cinnamomea and significant downregulation of several microRNAs and cancer stemness expression levels in brain and breast CSCs. More importantly, higher CD133 expression is associated with poor prognosis in glioblastoma and breast cancer patients. Conclusion Herein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.

Original languageEnglish
Pages (from-to)47-56
Number of pages10
JournalJournal of Ethnopharmacology
Volume207
DOIs
Publication statusPublished - Jul 31 2017

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Antrodia
Neoplastic Stem Cells
MicroRNAs
Radio
Neoplasms
Therapeutics
Mycelium
Human Genome
Glioblastoma
Breast Neoplasms
Cell Line
Adenocarcinoma
Leukemia, Monocytic, Acute
Hepatoblastoma
Foreskin
Squamous Cell Neoplasms
Polymerase Chain Reaction
Lung
Epithelial-Mesenchymal Transition
Chinese Traditional Medicine

Keywords

  • Antrodia cinnamomea
  • Cancer stem cell
  • Chemotherapy
  • Onco-microRNA
  • Radiotherapy

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Antrodia cinnamomea sensitizes radio-/chemo-therapy of cancer stem-like cells by modulating microRNA expression. / Su, Yu Kai; Shih, Ping Hsiao; Lee, Wei Hwa; Bamodu, Oluwaseun Adebayo; Wu, Alexander T.H.; Huang, Chun Chih; Tzeng, Yew Min; Hsiao, Michael; Yeh, Chi Tai; Lin, Chien Min.

In: Journal of Ethnopharmacology, Vol. 207, 31.07.2017, p. 47-56.

Research output: Contribution to journalArticle

Su, Yu Kai ; Shih, Ping Hsiao ; Lee, Wei Hwa ; Bamodu, Oluwaseun Adebayo ; Wu, Alexander T.H. ; Huang, Chun Chih ; Tzeng, Yew Min ; Hsiao, Michael ; Yeh, Chi Tai ; Lin, Chien Min. / Antrodia cinnamomea sensitizes radio-/chemo-therapy of cancer stem-like cells by modulating microRNA expression. In: Journal of Ethnopharmacology. 2017 ; Vol. 207. pp. 47-56.
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title = "Antrodia cinnamomea sensitizes radio-/chemo-therapy of cancer stem-like cells by modulating microRNA expression",
abstract = "Ethnopharmacological relevance The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention. However, the anti-CSC capability of A. Cinnamomea is not clear yet. Aim of the study To investigate the inhibitory effect of A. cinnamomea mycelium and extract on CSCs derived from various human cancer cell lines using our in-house therapeutics and human genome-wide miRNA screening panels. Materials and methods A broad range of human cancer cell lines, including the acute monocytic leukemia (THP-1), glioblastoma multiforme (GBM 8401), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), hepatoblastoma (HepG2), colorectal adenocarcinoma (SW620), and foreskin fibroblast (HS68), were exposed to A. cinnamomea in this study. CD133+ CSCs generated from the cell lines were characterized and isolated by flow cytometry, effect of chemo- and radiotherapy was assessed using the MTT assay, while the RT-PCR and human genome wide qRT-PCR determined the differential gene expression patterns. A comparative analysis of the anticancer effect of A. cinnamomea and Cisplatin, Taxol, or irradiation was also performed. Results Our results indicated that A. cinnamomea mycelium and its ethyl acetate extracts showed anti-proliferation effects against all types of CSCs, especially the lung, breast, and head and neck squamous cell carcinoma CSCs. Furthermore, CSCs treatment with A. cinnamomea combined with irradiation or chemotherapeutics demonstrated significant anti-cancer effect. We also established an association between the CSC-inhibitory effect of A. cinnamomea and significant downregulation of several microRNAs and cancer stemness expression levels in brain and breast CSCs. More importantly, higher CD133 expression is associated with poor prognosis in glioblastoma and breast cancer patients. Conclusion Herein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.",
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author = "Su, {Yu Kai} and Shih, {Ping Hsiao} and Lee, {Wei Hwa} and Bamodu, {Oluwaseun Adebayo} and Wu, {Alexander T.H.} and Huang, {Chun Chih} and Tzeng, {Yew Min} and Michael Hsiao and Yeh, {Chi Tai} and Lin, {Chien Min}",
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T1 - Antrodia cinnamomea sensitizes radio-/chemo-therapy of cancer stem-like cells by modulating microRNA expression

AU - Su, Yu Kai

AU - Shih, Ping Hsiao

AU - Lee, Wei Hwa

AU - Bamodu, Oluwaseun Adebayo

AU - Wu, Alexander T.H.

AU - Huang, Chun Chih

AU - Tzeng, Yew Min

AU - Hsiao, Michael

AU - Yeh, Chi Tai

AU - Lin, Chien Min

PY - 2017/7/31

Y1 - 2017/7/31

N2 - Ethnopharmacological relevance The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention. However, the anti-CSC capability of A. Cinnamomea is not clear yet. Aim of the study To investigate the inhibitory effect of A. cinnamomea mycelium and extract on CSCs derived from various human cancer cell lines using our in-house therapeutics and human genome-wide miRNA screening panels. Materials and methods A broad range of human cancer cell lines, including the acute monocytic leukemia (THP-1), glioblastoma multiforme (GBM 8401), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), hepatoblastoma (HepG2), colorectal adenocarcinoma (SW620), and foreskin fibroblast (HS68), were exposed to A. cinnamomea in this study. CD133+ CSCs generated from the cell lines were characterized and isolated by flow cytometry, effect of chemo- and radiotherapy was assessed using the MTT assay, while the RT-PCR and human genome wide qRT-PCR determined the differential gene expression patterns. A comparative analysis of the anticancer effect of A. cinnamomea and Cisplatin, Taxol, or irradiation was also performed. Results Our results indicated that A. cinnamomea mycelium and its ethyl acetate extracts showed anti-proliferation effects against all types of CSCs, especially the lung, breast, and head and neck squamous cell carcinoma CSCs. Furthermore, CSCs treatment with A. cinnamomea combined with irradiation or chemotherapeutics demonstrated significant anti-cancer effect. We also established an association between the CSC-inhibitory effect of A. cinnamomea and significant downregulation of several microRNAs and cancer stemness expression levels in brain and breast CSCs. More importantly, higher CD133 expression is associated with poor prognosis in glioblastoma and breast cancer patients. Conclusion Herein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.

AB - Ethnopharmacological relevance The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention. However, the anti-CSC capability of A. Cinnamomea is not clear yet. Aim of the study To investigate the inhibitory effect of A. cinnamomea mycelium and extract on CSCs derived from various human cancer cell lines using our in-house therapeutics and human genome-wide miRNA screening panels. Materials and methods A broad range of human cancer cell lines, including the acute monocytic leukemia (THP-1), glioblastoma multiforme (GBM 8401), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), hepatoblastoma (HepG2), colorectal adenocarcinoma (SW620), and foreskin fibroblast (HS68), were exposed to A. cinnamomea in this study. CD133+ CSCs generated from the cell lines were characterized and isolated by flow cytometry, effect of chemo- and radiotherapy was assessed using the MTT assay, while the RT-PCR and human genome wide qRT-PCR determined the differential gene expression patterns. A comparative analysis of the anticancer effect of A. cinnamomea and Cisplatin, Taxol, or irradiation was also performed. Results Our results indicated that A. cinnamomea mycelium and its ethyl acetate extracts showed anti-proliferation effects against all types of CSCs, especially the lung, breast, and head and neck squamous cell carcinoma CSCs. Furthermore, CSCs treatment with A. cinnamomea combined with irradiation or chemotherapeutics demonstrated significant anti-cancer effect. We also established an association between the CSC-inhibitory effect of A. cinnamomea and significant downregulation of several microRNAs and cancer stemness expression levels in brain and breast CSCs. More importantly, higher CD133 expression is associated with poor prognosis in glioblastoma and breast cancer patients. Conclusion Herein, we demonstrate the putative role of A. cinnamomea as an effective ethnopharmacologic therapeutic agent for cancer treatment.

KW - Antrodia cinnamomea

KW - Cancer stem cell

KW - Chemotherapy

KW - Onco-microRNA

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