Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation
Abstract Our previous studies demonstrated that KG-135, a quality-controlled red ginseng-specific formulation containing approximately equal amounts of three major ginsenosides (Rk1, Rg3 and Rg5), down-regulated G1 cyclin-dependent kinase in HeLa cells. In the present work, we have found that KG-135...
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| Veröffentlicht in: | Cancer letters 2010-08, Vol.294 (1), p.74-81 |
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| creator | Lee, Won-Hee Choi, Joon-Seok Kim, Hyun Young Park, Jeong-Hill Park, Byoung Duck Cho, Seung Ju Lee, Seung-Ki Surh, Young-Joon |
| description | Abstract Our previous studies demonstrated that KG-135, a quality-controlled red ginseng-specific formulation containing approximately equal amounts of three major ginsenosides (Rk1, Rg3 and Rg5), down-regulated G1 cyclin-dependent kinase in HeLa cells. In the present work, we have found that KG-135 potentates cytotoxicity of etoposide by modulating apoptotic signaling. Co-treatment of etoposide and KG-135 markedly elevated the expression and phosphorylation at the serine 15 residue of p53 as well as the cellular levels of Bax and p21Waf1/Cip1 . The increased accumulation and phosphorylation of p53 (Ser15) were attenuated by treatment of cells with wortmannin, a pan-phosphatidylinositol-3 kinase inhibitor. Moreover, co-treatment of etoposide and KG-135 enhanced mitochondrial localization of Bax. Our results indicate that etoposide-induced apoptosis in HeLa cells can be potentiated in the presence of KG-135 through a mechanism that involves the stabilization of p53 and the stimulation of Bax- and p21-mediated apoptotic signaling pathways. These findings suggest that KG-135 represents a useful candidate adjuvant for the treatment of cancers that could potentially minimize the adverse effects of current clinical chemotherapeutics. |
| doi_str_mv | 10.1016/j.canlet.2010.01.024 |
| format | Article |
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In the present work, we have found that KG-135 potentates cytotoxicity of etoposide by modulating apoptotic signaling. Co-treatment of etoposide and KG-135 markedly elevated the expression and phosphorylation at the serine 15 residue of p53 as well as the cellular levels of Bax and p21Waf1/Cip1 . The increased accumulation and phosphorylation of p53 (Ser15) were attenuated by treatment of cells with wortmannin, a pan-phosphatidylinositol-3 kinase inhibitor. Moreover, co-treatment of etoposide and KG-135 enhanced mitochondrial localization of Bax. Our results indicate that etoposide-induced apoptosis in HeLa cells can be potentiated in the presence of KG-135 through a mechanism that involves the stabilization of p53 and the stimulation of Bax- and p21-mediated apoptotic signaling pathways. These findings suggest that KG-135 represents a useful candidate adjuvant for the treatment of cancers that could potentially minimize the adverse effects of current clinical chemotherapeutics.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2010.01.024</identifier><identifier>PMID: 20226587</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Androstadienes - pharmacology ; Androstadienes - therapeutic use ; Apoptosis ; Apoptosis - drug effects ; bcl-2-Associated X Protein - metabolism ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cancer ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - pathology ; Cell cycle ; Cell Line, Tumor ; Chromatography ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; DNA damage ; Drug dosages ; Drug Synergism ; Etoposide ; Etoposide - pharmacology ; Female ; Ginseng ; Ginsenosides - pharmacology ; Ginsenosides - therapeutic use ; HeLa Cells - cytology ; HeLa Cells - drug effects ; HeLa Cells - metabolism ; Hematology, Oncology and Palliative Medicine ; Humans ; KG-135 ; Kinases ; Korea ; Liver Neoplasms - drug therapy ; Liver Neoplasms - pathology ; Medicine, East Asian Traditional ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondria - physiology ; Mycotoxins - pharmacology ; p53 ; Phosphorylation ; Phosphoserine - metabolism ; Proteins ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - pathology</subject><ispartof>Cancer letters, 2010-08, Vol.294 (1), p.74-81</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2010 Elsevier Ireland Ltd</rights><rights>Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Aug 1, 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-1e1ee11131120dc6111af1c099a05541819a043eea002e153548457bfe10e963</citedby><cites>FETCH-LOGICAL-c444t-1e1ee11131120dc6111af1c099a05541819a043eea002e153548457bfe10e963</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.2010.01.024$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20226587$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Won-Hee</creatorcontrib><creatorcontrib>Choi, Joon-Seok</creatorcontrib><creatorcontrib>Kim, Hyun Young</creatorcontrib><creatorcontrib>Park, Jeong-Hill</creatorcontrib><creatorcontrib>Park, Byoung Duck</creatorcontrib><creatorcontrib>Cho, Seung Ju</creatorcontrib><creatorcontrib>Lee, Seung-Ki</creatorcontrib><creatorcontrib>Surh, Young-Joon</creatorcontrib><title>Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract Our previous studies demonstrated that KG-135, a quality-controlled red ginseng-specific formulation containing approximately equal amounts of three major ginsenosides (Rk1, Rg3 and Rg5), down-regulated G1 cyclin-dependent kinase in HeLa cells. In the present work, we have found that KG-135 potentates cytotoxicity of etoposide by modulating apoptotic signaling. Co-treatment of etoposide and KG-135 markedly elevated the expression and phosphorylation at the serine 15 residue of p53 as well as the cellular levels of Bax and p21Waf1/Cip1 . The increased accumulation and phosphorylation of p53 (Ser15) were attenuated by treatment of cells with wortmannin, a pan-phosphatidylinositol-3 kinase inhibitor. Moreover, co-treatment of etoposide and KG-135 enhanced mitochondrial localization of Bax. Our results indicate that etoposide-induced apoptosis in HeLa cells can be potentiated in the presence of KG-135 through a mechanism that involves the stabilization of p53 and the stimulation of Bax- and p21-mediated apoptotic signaling pathways. These findings suggest that KG-135 represents a useful candidate adjuvant for the treatment of cancers that could potentially minimize the adverse effects of current clinical chemotherapeutics.</description><subject>Androstadienes - pharmacology</subject><subject>Androstadienes - therapeutic use</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Chromatography</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Drug dosages</subject><subject>Drug Synergism</subject><subject>Etoposide</subject><subject>Etoposide - pharmacology</subject><subject>Female</subject><subject>Ginseng</subject><subject>Ginsenosides - pharmacology</subject><subject>Ginsenosides - therapeutic use</subject><subject>HeLa Cells - cytology</subject><subject>HeLa Cells - drug effects</subject><subject>HeLa Cells - metabolism</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>KG-135</subject><subject>Kinases</subject><subject>Korea</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - pathology</subject><subject>Medicine, East Asian Traditional</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - physiology</subject><subject>Mycotoxins - pharmacology</subject><subject>p53</subject><subject>Phosphorylation</subject><subject>Phosphoserine - metabolism</subject><subject>Proteins</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - pathology</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk2LFDEQDaK44-o_EAl4tceq7qQ_LoIsuisOKLj3kElXa8ZMMpuklfFX-JNN76wKXjylUrx6r6peMfYUYY2A7cvd2mjvKK9rKCnANdTiHlth39VVN_Rwn62gAVE1fSPP2KOUdgAgRScfsrMa6rqVfbdiPz-GTD5bnW3wPEyccjiEZEeqrB9nQyPXh3DIJZW49fyKNpobci7x7ZGbUOVIOu8LBf9u8xf-_rLCRr7gmt_M2tl8rEzwOQbnClPK2o86jvZH-Xy2PpG_leJTiPvZ3fbwmD2YtEv05O49Z9dv31xfXFWbD5fvLl5vKiOEyBUSEiFig1jDaNoS6gkNDIMGKQX2WALREGmAmlA2UvRCdtuJEGhom3P2_ER7iOFmppTVLszRF0WFElpoO1kvKHFCmRhSijSpQ7R7HY8KQS0uqJ06uaAWFxSgKi6Usmd35PN2T-Ofot9rL4BXJwCVCb9ZiioZS75s20YyWY3B_k_hXwLjrLdGu690pPR3FpVqBerTcgnLISAsRwBD8wu89a_9</recordid><startdate>20100801</startdate><enddate>20100801</enddate><creator>Lee, Won-Hee</creator><creator>Choi, Joon-Seok</creator><creator>Kim, Hyun Young</creator><creator>Park, Jeong-Hill</creator><creator>Park, Byoung Duck</creator><creator>Cho, Seung Ju</creator><creator>Lee, Seung-Ki</creator><creator>Surh, Young-Joon</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></search><sort><creationdate>20100801</creationdate><title>Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation</title><author>Lee, Won-Hee ; Choi, Joon-Seok ; Kim, Hyun Young ; Park, Jeong-Hill ; Park, Byoung Duck ; Cho, Seung Ju ; Lee, Seung-Ki ; Surh, Young-Joon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-1e1ee11131120dc6111af1c099a05541819a043eea002e153548457bfe10e963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Androstadienes - pharmacology</topic><topic>Androstadienes - therapeutic use</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Chromatography</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>Drug dosages</topic><topic>Drug Synergism</topic><topic>Etoposide</topic><topic>Etoposide - pharmacology</topic><topic>Female</topic><topic>Ginseng</topic><topic>Ginsenosides - pharmacology</topic><topic>Ginsenosides - therapeutic use</topic><topic>HeLa Cells - cytology</topic><topic>HeLa Cells - drug effects</topic><topic>HeLa Cells - metabolism</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>KG-135</topic><topic>Kinases</topic><topic>Korea</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - pathology</topic><topic>Medicine, East Asian Traditional</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - physiology</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - physiology</topic><topic>Mycotoxins - pharmacology</topic><topic>p53</topic><topic>Phosphorylation</topic><topic>Phosphoserine - metabolism</topic><topic>Proteins</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Won-Hee</creatorcontrib><creatorcontrib>Choi, Joon-Seok</creatorcontrib><creatorcontrib>Kim, Hyun Young</creatorcontrib><creatorcontrib>Park, Jeong-Hill</creatorcontrib><creatorcontrib>Park, Byoung Duck</creatorcontrib><creatorcontrib>Cho, Seung Ju</creatorcontrib><creatorcontrib>Lee, Seung-Ki</creatorcontrib><creatorcontrib>Surh, Young-Joon</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><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Won-Hee</au><au>Choi, Joon-Seok</au><au>Kim, Hyun Young</au><au>Park, Jeong-Hill</au><au>Park, Byoung Duck</au><au>Cho, Seung Ju</au><au>Lee, Seung-Ki</au><au>Surh, Young-Joon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2010-08-01</date><risdate>2010</risdate><volume>294</volume><issue>1</issue><spage>74</spage><epage>81</epage><pages>74-81</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract Our previous studies demonstrated that KG-135, a quality-controlled red ginseng-specific formulation containing approximately equal amounts of three major ginsenosides (Rk1, Rg3 and Rg5), down-regulated G1 cyclin-dependent kinase in HeLa cells. In the present work, we have found that KG-135 potentates cytotoxicity of etoposide by modulating apoptotic signaling. Co-treatment of etoposide and KG-135 markedly elevated the expression and phosphorylation at the serine 15 residue of p53 as well as the cellular levels of Bax and p21Waf1/Cip1 . The increased accumulation and phosphorylation of p53 (Ser15) were attenuated by treatment of cells with wortmannin, a pan-phosphatidylinositol-3 kinase inhibitor. Moreover, co-treatment of etoposide and KG-135 enhanced mitochondrial localization of Bax. Our results indicate that etoposide-induced apoptosis in HeLa cells can be potentiated in the presence of KG-135 through a mechanism that involves the stabilization of p53 and the stimulation of Bax- and p21-mediated apoptotic signaling pathways. These findings suggest that KG-135 represents a useful candidate adjuvant for the treatment of cancers that could potentially minimize the adverse effects of current clinical chemotherapeutics.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>20226587</pmid><doi>10.1016/j.canlet.2010.01.024</doi><tpages>8</tpages></addata></record> |
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| ispartof | Cancer letters, 2010-08, Vol.294 (1), p.74-81 |
| issn | 0304-3835 1872-7980 |
| language | eng |
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| subjects | Androstadienes - pharmacology Androstadienes - therapeutic use Apoptosis Apoptosis - drug effects bcl-2-Associated X Protein - metabolism Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cancer Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - pathology Cell cycle Cell Line, Tumor Chromatography Cytotoxicity Deoxyribonucleic acid DNA DNA damage Drug dosages Drug Synergism Etoposide Etoposide - pharmacology Female Ginseng Ginsenosides - pharmacology Ginsenosides - therapeutic use HeLa Cells - cytology HeLa Cells - drug effects HeLa Cells - metabolism Hematology, Oncology and Palliative Medicine Humans KG-135 Kinases Korea Liver Neoplasms - drug therapy Liver Neoplasms - pathology Medicine, East Asian Traditional Membrane Potentials - drug effects Membrane Potentials - physiology Mitochondria - drug effects Mitochondria - metabolism Mitochondria - physiology Mycotoxins - pharmacology p53 Phosphorylation Phosphoserine - metabolism Proteins Stomach Neoplasms - drug therapy Stomach Neoplasms - pathology |
| title | Potentiation of etoposide-induced apoptosis in HeLa cells by co-treatment with KG-135, a quality-controlled standardized ginsenoside formulation |
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