Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells
In a search for new anticancer agents, we identified a novel compound polyphyllin D (PD) (diosgenyl α- l-rhamnopyranosyl-(1→2)-(α- l-arabinofuranosyl)-(1→4)]-[β- d-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line Hep...
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| Veröffentlicht in: | Cancer letters 2005-01, Vol.217 (2), p.203-211 |
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| creator | Yuen-Nei Cheung, Jenny Chik-Ying Ong, Rose Suen, Yick-Keung Ooi, Vincent Nai-Ching Wong, Henry Chung-Wai Mak, Thomas Fung, Kwok-Pui Yu, Biao Kong, Siu-Kai |
| description | In a search for new anticancer agents, we identified a novel compound polyphyllin D (PD) (diosgenyl α-
l-rhamnopyranosyl-(1→2)-(α-
l-arabinofuranosyl)-(1→4)]-[β-
d-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line HepG2 derivative with drug resistance (R-HepG2). PD is a saponin originally found in a tradition Chinese medicinal herb
Paris polyphylla. It has been used to treat liver cancer in China for many years. We evaluated the cell-killing mechanisms of this compound in R-HepG2 and its parental cells. The mitochondrial apoptotic pathway was found to be involved in the PD-induced apoptosis because PD elicited depolarization of mitochondrial transmembrane potential (Δ
Ψm), generation of H
2O
2, as well as release of cytochrome
c and apoptosis-inducing factor in a dose- and time-dependent manner. In conclusion, we show for the first time that PD is a potent anticancer agent that can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction. |
| doi_str_mv | 10.1016/j.canlet.2004.06.042 |
| format | Article |
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l-rhamnopyranosyl-(1→2)-(α-
l-arabinofuranosyl)-(1→4)]-[β-
d-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line HepG2 derivative with drug resistance (R-HepG2). PD is a saponin originally found in a tradition Chinese medicinal herb
Paris polyphylla. It has been used to treat liver cancer in China for many years. We evaluated the cell-killing mechanisms of this compound in R-HepG2 and its parental cells. The mitochondrial apoptotic pathway was found to be involved in the PD-induced apoptosis because PD elicited depolarization of mitochondrial transmembrane potential (Δ
Ψm), generation of H
2O
2, as well as release of cytochrome
c and apoptosis-inducing factor in a dose- and time-dependent manner. In conclusion, we show for the first time that PD is a potent anticancer agent that can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2004.06.042</identifier><identifier>PMID: 15617838</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Apoptosis Inducing Factor ; Blotting, Western ; Cancer therapies ; Carcinoma, Hepatocellular - metabolism ; Cell Line, Tumor ; Cytochromes c - drug effects ; Cytochromes c - metabolism ; Cytotoxicity ; Deoxyribonucleic acid ; Diosgenin - analogs & derivatives ; Diosgenin - pharmacology ; DNA ; Drug resistance ; Drug Resistance, Neoplasm ; Flavoproteins - drug effects ; Flavoproteins - metabolism ; Flow Cytometry ; HepG2 ; Humans ; Liver cancer ; Membrane Proteins - drug effects ; Membrane Proteins - metabolism ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - pathology ; Molecular weight ; Polyphyllin D ; Proteins ; Reactive Oxygen Species - metabolism ; Saponins</subject><ispartof>Cancer letters, 2005-01, Vol.217 (2), p.203-211</ispartof><rights>2004 Elsevier Ireland Ltd</rights><rights>Copyright Elsevier Limited Jan 20, 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-843c981c46c77ee98ddf3f9eef272420847af794d5c966a0648d13d1617360983</citedby><cites>FETCH-LOGICAL-c454t-843c981c46c77ee98ddf3f9eef272420847af794d5c966a0648d13d1617360983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2004.06.042$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15617838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuen-Nei Cheung, Jenny</creatorcontrib><creatorcontrib>Chik-Ying Ong, Rose</creatorcontrib><creatorcontrib>Suen, Yick-Keung</creatorcontrib><creatorcontrib>Ooi, Vincent</creatorcontrib><creatorcontrib>Nai-Ching Wong, Henry</creatorcontrib><creatorcontrib>Chung-Wai Mak, Thomas</creatorcontrib><creatorcontrib>Fung, Kwok-Pui</creatorcontrib><creatorcontrib>Yu, Biao</creatorcontrib><creatorcontrib>Kong, Siu-Kai</creatorcontrib><title>Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>In a search for new anticancer agents, we identified a novel compound polyphyllin D (PD) (diosgenyl α-
l-rhamnopyranosyl-(1→2)-(α-
l-arabinofuranosyl)-(1→4)]-[β-
d-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line HepG2 derivative with drug resistance (R-HepG2). PD is a saponin originally found in a tradition Chinese medicinal herb
Paris polyphylla. It has been used to treat liver cancer in China for many years. We evaluated the cell-killing mechanisms of this compound in R-HepG2 and its parental cells. The mitochondrial apoptotic pathway was found to be involved in the PD-induced apoptosis because PD elicited depolarization of mitochondrial transmembrane potential (Δ
Ψm), generation of H
2O
2, as well as release of cytochrome
c and apoptosis-inducing factor in a dose- and time-dependent manner. In conclusion, we show for the first time that PD is a potent anticancer agent that can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.</description><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Apoptosis Inducing Factor</subject><subject>Blotting, Western</subject><subject>Cancer therapies</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cytochromes c - drug effects</subject><subject>Cytochromes c - metabolism</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>Diosgenin - analogs & derivatives</subject><subject>Diosgenin - pharmacology</subject><subject>DNA</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Flavoproteins - drug effects</subject><subject>Flavoproteins - metabolism</subject><subject>Flow Cytometry</subject><subject>HepG2</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Membrane Proteins - drug effects</subject><subject>Membrane Proteins - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - pathology</subject><subject>Molecular weight</subject><subject>Polyphyllin D</subject><subject>Proteins</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Saponins</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rFEEQhhuJmDX6D4IMBLzNWD39fRFk1SQQ0ENybtrumtjL7PTYPSPsv7eXXRA8eCoonrfq5SHkmkJHgcoPu867acSl6wF4B7ID3r8gG6pV3yqj4YJsgAFvmWbikrwuZQcAgivxilxSIanSTG_I_fc0Huafh3GMU_O5iaVxzZwWnJbGzWleUqmrOIXVY66zCXl9bjPW7eIqc4fzbd94HMfyhrwc3Fjw7XlekaevXx63d-3Dt9v77aeH1nPBl1Zz5o2mnkuvFKLRIQxsMIhDr3reg-bKDcrwILyR0oHkOlAWaC3MJBjNrsj70905p18rlsXuYzk2cBOmtVipGFOGigre_APu0pqn2s1SAYJJA0JWip8on1MpGQc757h3-WAp2KNou7Mn0fYo2oK0VXSNvTsfX3_sMfwNnc1W4OMJwOrid8Rsi484eQwxo19sSPH_H_4ANSqOug</recordid><startdate>20050120</startdate><enddate>20050120</enddate><creator>Yuen-Nei Cheung, Jenny</creator><creator>Chik-Ying Ong, Rose</creator><creator>Suen, Yick-Keung</creator><creator>Ooi, Vincent</creator><creator>Nai-Ching Wong, Henry</creator><creator>Chung-Wai Mak, Thomas</creator><creator>Fung, Kwok-Pui</creator><creator>Yu, Biao</creator><creator>Kong, Siu-Kai</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20050120</creationdate><title>Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells</title><author>Yuen-Nei Cheung, Jenny ; Chik-Ying Ong, Rose ; Suen, Yick-Keung ; Ooi, Vincent ; Nai-Ching Wong, Henry ; Chung-Wai Mak, Thomas ; Fung, Kwok-Pui ; Yu, Biao ; Kong, Siu-Kai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-843c981c46c77ee98ddf3f9eef272420847af794d5c966a0648d13d1617360983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Apoptosis Inducing Factor</topic><topic>Blotting, Western</topic><topic>Cancer therapies</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cytochromes c - drug effects</topic><topic>Cytochromes c - metabolism</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>Diosgenin - analogs & derivatives</topic><topic>Diosgenin - pharmacology</topic><topic>DNA</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm</topic><topic>Flavoproteins - drug effects</topic><topic>Flavoproteins - metabolism</topic><topic>Flow Cytometry</topic><topic>HepG2</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Membrane Proteins - drug effects</topic><topic>Membrane Proteins - metabolism</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - pathology</topic><topic>Molecular weight</topic><topic>Polyphyllin D</topic><topic>Proteins</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Saponins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuen-Nei Cheung, Jenny</creatorcontrib><creatorcontrib>Chik-Ying Ong, Rose</creatorcontrib><creatorcontrib>Suen, Yick-Keung</creatorcontrib><creatorcontrib>Ooi, Vincent</creatorcontrib><creatorcontrib>Nai-Ching Wong, Henry</creatorcontrib><creatorcontrib>Chung-Wai Mak, Thomas</creatorcontrib><creatorcontrib>Fung, Kwok-Pui</creatorcontrib><creatorcontrib>Yu, Biao</creatorcontrib><creatorcontrib>Kong, Siu-Kai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuen-Nei Cheung, Jenny</au><au>Chik-Ying Ong, Rose</au><au>Suen, Yick-Keung</au><au>Ooi, Vincent</au><au>Nai-Ching Wong, Henry</au><au>Chung-Wai Mak, Thomas</au><au>Fung, Kwok-Pui</au><au>Yu, Biao</au><au>Kong, Siu-Kai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2005-01-20</date><risdate>2005</risdate><volume>217</volume><issue>2</issue><spage>203</spage><epage>211</epage><pages>203-211</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>In a search for new anticancer agents, we identified a novel compound polyphyllin D (PD) (diosgenyl α-
l-rhamnopyranosyl-(1→2)-(α-
l-arabinofuranosyl)-(1→4)]-[β-
d-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line HepG2 derivative with drug resistance (R-HepG2). PD is a saponin originally found in a tradition Chinese medicinal herb
Paris polyphylla. It has been used to treat liver cancer in China for many years. We evaluated the cell-killing mechanisms of this compound in R-HepG2 and its parental cells. The mitochondrial apoptotic pathway was found to be involved in the PD-induced apoptosis because PD elicited depolarization of mitochondrial transmembrane potential (Δ
Ψm), generation of H
2O
2, as well as release of cytochrome
c and apoptosis-inducing factor in a dose- and time-dependent manner. In conclusion, we show for the first time that PD is a potent anticancer agent that can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>15617838</pmid><doi>10.1016/j.canlet.2004.06.042</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0304-3835 |
| ispartof | Cancer letters, 2005-01, Vol.217 (2), p.203-211 |
| issn | 0304-3835 1872-7980 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Apoptosis Apoptosis - drug effects Apoptosis - physiology Apoptosis Inducing Factor Blotting, Western Cancer therapies Carcinoma, Hepatocellular - metabolism Cell Line, Tumor Cytochromes c - drug effects Cytochromes c - metabolism Cytotoxicity Deoxyribonucleic acid Diosgenin - analogs & derivatives Diosgenin - pharmacology DNA Drug resistance Drug Resistance, Neoplasm Flavoproteins - drug effects Flavoproteins - metabolism Flow Cytometry HepG2 Humans Liver cancer Membrane Proteins - drug effects Membrane Proteins - metabolism Mitochondria Mitochondria - drug effects Mitochondria - pathology Molecular weight Polyphyllin D Proteins Reactive Oxygen Species - metabolism Saponins |
| title | Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells |
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