4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest
Identifieur interne : 001B66 ( Main/Merge ); précédent : 001B65; suivant : 001B674β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest
Auteurs : Ching-Yu Yen [Taïwan] ; Chien-Chih Chiu [Taïwan] ; Fang-Rong Chang [Taïwan] ; Jeff Yi-Fu Chen [Taïwan] ; Chi-Ching Hwang [Taïwan] ; You-Cheng Hseu [Taïwan] ; Hsin-Ling Yang [Taïwan] ; Alan Yueh-Luen Lee [Taïwan] ; Ming-Tz Tsai [Taïwan] ; Zong-Lun Guo [Taïwan] ; Yu-Shan Cheng [Taïwan] ; Yin-Chang Liu [Taïwan] ; Yu-Hsuan Lan [Taïwan] ; Yu-Ching Chang [Taïwan] ; Ying-Chin Ko [Taïwan] ; Hsueh-Wei Chang [Taïwan] ; Yang-Chang Wu [Taïwan]Source :
- BMC Cancer [ 1471-2407 ] ; 2010.
Abstract
The crude extract of the fruit bearing plant,
Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.
It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (
In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.
Url:
DOI: 10.1186/1471-2407-10-46
PubMed: 20167063
PubMed Central: 2830937
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(golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G<sub>2</sub>
/M arrest</title>
<author><name sortKey="Yen, Ching Yu" sort="Yen, Ching Yu" uniqKey="Yen C" first="Ching-Yu" last="Yen">Ching-Yu Yen</name>
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<author><name sortKey="Ko, Ying Chin" sort="Ko, Ying Chin" uniqKey="Ko Y" first="Ying-Chin" last="Ko">Ying-Chin Ko</name>
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<affiliation wicri:level="1"><nlm:aff id="I14">Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
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<affiliation wicri:level="1"><nlm:aff id="I15">Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">4β-Hydroxywithanolide E from <italic>Physalis peruviana </italic>
(golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G<sub>2</sub>
/M arrest</title>
<author><name sortKey="Yen, Ching Yu" sort="Yen, Ching Yu" uniqKey="Yen C" first="Ching-Yu" last="Yen">Ching-Yu Yen</name>
<affiliation wicri:level="1"><nlm:aff id="I1">Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan</wicri:regionArea>
<wicri:noRegion>Tainan</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I2">School of Dentistry, Taipei Medical University, Taipei, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>School of Dentistry, Taipei Medical University, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chiu, Chien Chih" sort="Chiu, Chien Chih" uniqKey="Chiu C" first="Chien-Chih" last="Chiu">Chien-Chih Chiu</name>
<affiliation wicri:level="1"><nlm:aff id="I3">Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Biotechnology, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I15">Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chang, Fang Rong" sort="Chang, Fang Rong" uniqKey="Chang F" first="Fang-Rong" last="Chang">Fang-Rong Chang</name>
<affiliation wicri:level="1"><nlm:aff id="I4">Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I15">Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
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<author><name sortKey="Chen, Jeff Yi Fu" sort="Chen, Jeff Yi Fu" uniqKey="Chen J" first="Jeff Yi-Fu" last="Chen">Jeff Yi-Fu Chen</name>
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<author><name sortKey="Hwang, Chi Ching" sort="Hwang, Chi Ching" uniqKey="Hwang C" first="Chi-Ching" last="Hwang">Chi-Ching Hwang</name>
<affiliation wicri:level="1"><nlm:aff id="I5">Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Biochemistry, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Hseu, You Cheng" sort="Hseu, You Cheng" uniqKey="Hseu Y" first="You-Cheng" last="Hseu">You-Cheng Hseu</name>
<affiliation wicri:level="1"><nlm:aff id="I6">Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung</wicri:regionArea>
<wicri:noRegion>Taichung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yang, Hsin Ling" sort="Yang, Hsin Ling" uniqKey="Yang H" first="Hsin-Ling" last="Yang">Hsin-Ling Yang</name>
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<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Institute of Nutrition, China Medical University, Taichung</wicri:regionArea>
<wicri:noRegion>Taichung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lee, Alan Yueh Luen" sort="Lee, Alan Yueh Luen" uniqKey="Lee A" first="Alan Yueh-Luen" last="Lee">Alan Yueh-Luen Lee</name>
<affiliation wicri:level="1"><nlm:aff id="I3">Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Biotechnology, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I15">Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tsai, Ming Tz" sort="Tsai, Ming Tz" uniqKey="Tsai M" first="Ming-Tz" last="Tsai">Ming-Tz Tsai</name>
<affiliation wicri:level="1"><nlm:aff id="I14">Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Guo, Zong Lun" sort="Guo, Zong Lun" uniqKey="Guo Z" first="Zong-Lun" last="Guo">Zong-Lun Guo</name>
<affiliation wicri:level="1"><nlm:aff id="I3">Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Biotechnology, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cheng, Yu Shan" sort="Cheng, Yu Shan" uniqKey="Cheng Y" first="Yu-Shan" last="Cheng">Yu-Shan Cheng</name>
<affiliation wicri:level="1"><nlm:aff id="I14">Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liu, Yin Chang" sort="Liu, Yin Chang" uniqKey="Liu Y" first="Yin-Chang" last="Liu">Yin-Chang Liu</name>
<affiliation wicri:level="1"><nlm:aff id="I8">Institute of Molecular Medicine, National Tsing-Hua University, Hsinchu, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Institute of Molecular Medicine, National Tsing-Hua University, Hsinchu</wicri:regionArea>
<wicri:noRegion>Hsinchu</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I9">Department of Life Science, National Tsing-Hua University, Hsinchu, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Life Science, National Tsing-Hua University, Hsinchu</wicri:regionArea>
<wicri:noRegion>Hsinchu</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lan, Yu Hsuan" sort="Lan, Yu Hsuan" uniqKey="Lan Y" first="Yu-Hsuan" last="Lan">Yu-Hsuan Lan</name>
<affiliation wicri:level="1"><nlm:aff id="I10">School of Pharmacy, China Medical University, Taichung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>School of Pharmacy, China Medical University, Taichung</wicri:regionArea>
<wicri:noRegion>Taichung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chang, Yu Ching" sort="Chang, Yu Ching" uniqKey="Chang Y" first="Yu-Ching" last="Chang">Yu-Ching Chang</name>
<affiliation wicri:level="1"><nlm:aff id="I11">Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Agricultural Biotechnology Research Center, Academia Sinica, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ko, Ying Chin" sort="Ko, Ying Chin" uniqKey="Ko Y" first="Ying-Chin" last="Ko">Ying-Chin Ko</name>
<affiliation wicri:level="1"><nlm:aff id="I12">Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I13">Graduate Institute of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Graduate Institute of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I15">Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chang, Hsueh Wei" sort="Chang, Hsueh Wei" uniqKey="Chang H" first="Hsueh-Wei" last="Chang">Hsueh-Wei Chang</name>
<affiliation wicri:level="1"><nlm:aff id="I4">Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I14">Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I15">Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wu, Yang Chang" sort="Wu, Yang Chang" uniqKey="Wu Y" first="Yang-Chang" last="Wu">Yang-Chang Wu</name>
<affiliation wicri:level="1"><nlm:aff id="I4">Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="I15">Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung</wicri:regionArea>
<wicri:noRegion>Kaohsiung</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">BMC Cancer</title>
<idno type="eISSN">1471-2407</idno>
<imprint><date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>The crude extract of the fruit bearing plant, <italic>Physalis peruviana </italic>
(golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.</p>
</sec>
<sec><title>Methods</title>
<p>Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.</p>
</sec>
<sec><title>Results</title>
<p>It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (<italic>p </italic>
< 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (<italic>p </italic>
< 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC<sub>50</sub>
) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G<sub>1 </sub>
accumulation and slight arrest at the G<sub>2</sub>
/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G<sub>2</sub>
/M arrest for H1299 cells treated with 5 μg/mL for 24 h.</p>
</sec>
<sec><title>Conclusions</title>
<p>In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.</p>
</sec>
</div>
</front>
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