Ergosterol purified from medicinal mushroom Amauroderma rude inhibits cancer growth in vitro and in vivo by up-regulating multiple tumor suppressors

We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti...

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Published inOncotarget Vol. 6; no. 19; pp. 17832 - 17846
Main Authors Li, Xiangmin, Wu, Qingping, Xie, Yizhen, Ding, Yinrun, Du, William W., Sdiri, Mouna, Yang, Burton B.
Format Journal Article
LanguageEnglish
Published United States Impact Journals LLC 10.07.2015
Subjects
Agaricales - chemistry
Animals
Antineoplastic Agents - pharmacology
Blotting, Western
Cell Death - drug effects
Cell Line, Tumor
Cell Movement - drug effects
Cell Survival - drug effects
Ergosterol - pharmacology
Flow Cytometry
Genes, Tumor Suppressor - drug effects
Humans
Mice
Neoplasms, Experimental - drug therapy
Phytotherapy - methods
Plant Extracts - pharmacology
Real-Time Polymerase Chain Reaction
Research Paper
Up-Regulation
Online AccessGet full text

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Abstract We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography,and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR,which was expressed at the highest level in Amauroderma rude compared with other medicinal mushrooms tested. We found that ergosterol induced cancer cell death,which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol-mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL,BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude, which activated the apoptotic signal pathway. Ergosterol may serve as a potential lead for cancer therapy.
AbstractList We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography,and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR,which was expressed at the highest level in Amauroderma rude compared with other medicinal mushrooms tested. We found that ergosterol induced cancer cell death,which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol-mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL,BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude, which activated the apoptotic signal pathway. Ergosterol may serve as a potential lead for cancer therapy.We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography,and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR,which was expressed at the highest level in Amauroderma rude compared with other medicinal mushrooms tested. We found that ergosterol induced cancer cell death,which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol-mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL,BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude, which activated the apoptotic signal pathway. Ergosterol may serve as a potential lead for cancer therapy.
We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography, and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR, which was expressed at the highest level in Amauroderma rude compared with other medicinal mushrooms tested. We found that ergosterol induced cancer cell death, which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol-mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL, BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude , which activated the apoptotic signal pathway. Ergosterol may serve as a potential lead for cancer therapy.
We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography,and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR,which was expressed at the highest level in Amauroderma rude compared with other medicinal mushrooms tested. We found that ergosterol induced cancer cell death,which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol-mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL,BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude, which activated the apoptotic signal pathway. Ergosterol may serve as a potential lead for cancer therapy.
Author Wu, Qingping
Sdiri, Mouna
Ding, Yinrun
Li, Xiangmin
Xie, Yizhen
Yang, Burton B.
Du, William W.
AuthorAffiliation 1 School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, PR China
2 State Key Laboratory of Applied Microbiology Southern China (The Ministry-Province Joint Development), Guangdong Institute of Microbiology, Guangzhou, 510070, PR China
4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N3M5, Canada
3 Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, M4N3M5, Canada
AuthorAffiliation_xml – name: 3 Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, M4N3M5, Canada
– name: 2 State Key Laboratory of Applied Microbiology Southern China (The Ministry-Province Joint Development), Guangdong Institute of Microbiology, Guangzhou, 510070, PR China
– name: 1 School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, PR China
– name: 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N3M5, Canada
Author_xml – sequence: 1
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  surname: Li
  fullname: Li, Xiangmin
  organization: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, PR China, State Key Laboratory of Applied Microbiology Southern China (The Ministry-Province Joint Development), Guangdong Institute of Microbiology, Guangzhou, 510070, PR China, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, M4N3M5, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N3M5, Canada
– sequence: 2
  givenname: Qingping
  surname: Wu
  fullname: Wu, Qingping
  organization: State Key Laboratory of Applied Microbiology Southern China (The Ministry-Province Joint Development), Guangdong Institute of Microbiology, Guangzhou, 510070, PR China
– sequence: 3
  givenname: Yizhen
  surname: Xie
  fullname: Xie, Yizhen
  organization: State Key Laboratory of Applied Microbiology Southern China (The Ministry-Province Joint Development), Guangdong Institute of Microbiology, Guangzhou, 510070, PR China
– sequence: 4
  givenname: Yinrun
  surname: Ding
  fullname: Ding, Yinrun
  organization: State Key Laboratory of Applied Microbiology Southern China (The Ministry-Province Joint Development), Guangdong Institute of Microbiology, Guangzhou, 510070, PR China
– sequence: 5
  givenname: William W.
  surname: Du
  fullname: Du, William W.
  organization: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, M4N3M5, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N3M5, Canada
– sequence: 6
  givenname: Mouna
  surname: Sdiri
  fullname: Sdiri, Mouna
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– sequence: 7
  givenname: Burton B.
  surname: Yang
  fullname: Yang, Burton B.
  organization: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, M4N3M5, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N3M5, Canada
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Snippet We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract...
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pubmed
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StartPage 17832
SubjectTerms Agaricales - chemistry
Animals
Antineoplastic Agents - pharmacology
Blotting, Western
Cell Death - drug effects
Cell Line, Tumor
Cell Movement - drug effects
Cell Survival - drug effects
Ergosterol - pharmacology
Flow Cytometry
Genes, Tumor Suppressor - drug effects
Humans
Mice
Neoplasms, Experimental - drug therapy
Phytotherapy - methods
Plant Extracts - pharmacology
Real-Time Polymerase Chain Reaction
Research Paper
Up-Regulation
Title Ergosterol purified from medicinal mushroom Amauroderma rude inhibits cancer growth in vitro and in vivo by up-regulating multiple tumor suppressors
URI https://www.ncbi.nlm.nih.gov/pubmed/26098777
https://www.proquest.com/docview/1719976094
https://pubmed.ncbi.nlm.nih.gov/PMC4627349
Volume 6
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