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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 : 001B67

4β-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 :

RBID : PMC:2830937

Abstract

Background

The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.

Methods

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.

Results

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 (p < 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (p < 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) 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-G1 accumulation and slight arrest at the G2/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 G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h.

Conclusions

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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PMC:2830937

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<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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<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>
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<nlm:aff id="I1">Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan, Taiwan</nlm:aff>
<country xml:lang="fr">Taïwan</country>
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<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>
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</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>
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</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>
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</affiliation>
</author>
<author>
<name sortKey="Chang, Fang Rong" sort="Chang, Fang Rong" uniqKey="Chang F" first="Fang-Rong" last="Chang">Fang-Rong Chang</name>
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<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>
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</author>
<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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<nlm:aff id="I3">Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan</nlm:aff>
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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>
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<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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</author>
<author>
<name sortKey="Hseu, You Cheng" sort="Hseu, You Cheng" uniqKey="Hseu Y" first="You-Cheng" last="Hseu">You-Cheng Hseu</name>
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<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>
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<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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<nlm:aff id="I7">Institute of Nutrition, China Medical University, Taichung, Taiwan</nlm:aff>
<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>
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<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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