Pennogenyl Saponins from Paris quadrifolia L. Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells
Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present...
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| description | Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present study reports on the evaluation of cytotoxic effects and explanation of the molecular mechanisms of action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To determine the viability of the cells treated with the compounds we used real-time cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2 strongly inhibited the tumor cells growth with IC50 values of 1.11 ± 0.04 μg/ml and 0.87 ± 0.05 μg/ml, respectively. The flow cytometry analysis indicated that the two compounds induced apoptosis in a dose-dependent manner and decreased mitochondrial membrane potential in HeLa cells in the early stage of apoptosis. Quantitative PCR and Western Blot analysis showed that the two saponins significantly increased mRNA expression of FADD and BID as well as induced caspase-8 via increased of procaspase-8 processing in the treated cells. The results of this study suggest that both the extrinsic death receptor and intrinsic mitochondrial pathways are involved in the programmed cell death. |
| doi_str_mv | 10.1371/journal.pone.0135993 |
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Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Stefanowicz-Hajduk, Justyna ; Bartoszewski, Rafal ; Bartoszewska, Sylwia ; Kochan, Kinga ; Adamska, Anna ; Kosiński, Igor ; Ochocka, J Renata</creator><creatorcontrib>Stefanowicz-Hajduk, Justyna ; Bartoszewski, Rafal ; Bartoszewska, Sylwia ; Kochan, Kinga ; Adamska, Anna ; Kosiński, Igor ; Ochocka, J Renata</creatorcontrib><description>Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present study reports on the evaluation of cytotoxic effects and explanation of the molecular mechanisms of action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To determine the viability of the cells treated with the compounds we used real-time cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2 strongly inhibited the tumor cells growth with IC50 values of 1.11 ± 0.04 μg/ml and 0.87 ± 0.05 μg/ml, respectively. The flow cytometry analysis indicated that the two compounds induced apoptosis in a dose-dependent manner and decreased mitochondrial membrane potential in HeLa cells in the early stage of apoptosis. Quantitative PCR and Western Blot analysis showed that the two saponins significantly increased mRNA expression of FADD and BID as well as induced caspase-8 via increased of procaspase-8 processing in the treated cells. The results of this study suggest that both the extrinsic death receptor and intrinsic mitochondrial pathways are involved in the programmed cell death.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0135993</identifier><identifier>PMID: 26295969</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Analysis ; Anticancer properties ; Antineoplastic Agents, Phytogenic - isolation & purification ; Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis ; Apoptosis - drug effects ; BH3 Interacting Domain Death Agonist Protein - agonists ; BH3 Interacting Domain Death Agonist Protein - genetics ; BH3 Interacting Domain Death Agonist Protein - metabolism ; Biological properties ; Biology ; Cancer therapies ; Caspase ; Caspase 8 - genetics ; Caspase 8 - metabolism ; Caspase-8 ; Cell cycle ; Cell death ; Cell proliferation ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Cervical cancer ; Cervix ; Cytotoxicity ; Drug therapy ; Experiments ; FADD protein ; Fas-Associated Death Domain Protein - agonists ; Fas-Associated Death Domain Protein - genetics ; Fas-Associated Death Domain Protein - metabolism ; Female ; Flow cytometry ; Formulations ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; HeLa Cells ; Humans ; Inhibitory Concentration 50 ; Liliaceae - chemistry ; Medical research ; Membrane potential ; Membrane Potential, Mitochondrial - drug effects ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondria - pathology ; Molecular chains ; Molecular modelling ; Penicillin ; Pharmaceuticals ; Pharmacology ; Physiological aspects ; Rhizome - chemistry ; Rhizomes ; Saponins ; Saponins - isolation & purification ; Saponins - pharmacology ; Signal Transduction ; Tumor cells</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0135993-e0135993</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Stefanowicz-Hajduk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Stefanowicz-Hajduk et al 2015 Stefanowicz-Hajduk et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-dec75b555e5b374d3405896c3c8b39b243014f6e83c85d4803a3bac040e1a73c3</citedby><cites>FETCH-LOGICAL-c692t-dec75b555e5b374d3405896c3c8b39b243014f6e83c85d4803a3bac040e1a73c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546673/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546673/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26295969$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stefanowicz-Hajduk, Justyna</creatorcontrib><creatorcontrib>Bartoszewski, Rafal</creatorcontrib><creatorcontrib>Bartoszewska, Sylwia</creatorcontrib><creatorcontrib>Kochan, Kinga</creatorcontrib><creatorcontrib>Adamska, Anna</creatorcontrib><creatorcontrib>Kosiński, Igor</creatorcontrib><creatorcontrib>Ochocka, J Renata</creatorcontrib><title>Pennogenyl Saponins from Paris quadrifolia L. Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present study reports on the evaluation of cytotoxic effects and explanation of the molecular mechanisms of action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To determine the viability of the cells treated with the compounds we used real-time cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2 strongly inhibited the tumor cells growth with IC50 values of 1.11 ± 0.04 μg/ml and 0.87 ± 0.05 μg/ml, respectively. 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drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Cytotoxicity</subject><subject>Drug therapy</subject><subject>Experiments</subject><subject>FADD protein</subject><subject>Fas-Associated Death Domain Protein - agonists</subject><subject>Fas-Associated Death Domain Protein - genetics</subject><subject>Fas-Associated Death Domain Protein - metabolism</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Formulations</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Liliaceae - chemistry</subject><subject>Medical research</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - 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Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-21</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0135993</spage><epage>e0135993</epage><pages>e0135993-e0135993</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present study reports on the evaluation of cytotoxic effects and explanation of the molecular mechanisms of action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To determine the viability of the cells treated with the compounds we used real-time cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2 strongly inhibited the tumor cells growth with IC50 values of 1.11 ± 0.04 μg/ml and 0.87 ± 0.05 μg/ml, respectively. The flow cytometry analysis indicated that the two compounds induced apoptosis in a dose-dependent manner and decreased mitochondrial membrane potential in HeLa cells in the early stage of apoptosis. Quantitative PCR and Western Blot analysis showed that the two saponins significantly increased mRNA expression of FADD and BID as well as induced caspase-8 via increased of procaspase-8 processing in the treated cells. The results of this study suggest that both the extrinsic death receptor and intrinsic mitochondrial pathways are involved in the programmed cell death.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26295969</pmid><doi>10.1371/journal.pone.0135993</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1719000197 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adenocarcinoma Analysis Anticancer properties Antineoplastic Agents, Phytogenic - isolation & purification Antineoplastic Agents, Phytogenic - pharmacology Apoptosis Apoptosis - drug effects BH3 Interacting Domain Death Agonist Protein - agonists BH3 Interacting Domain Death Agonist Protein - genetics BH3 Interacting Domain Death Agonist Protein - metabolism Biological properties Biology Cancer therapies Caspase Caspase 8 - genetics Caspase 8 - metabolism Caspase-8 Cell cycle Cell death Cell proliferation Cell Proliferation - drug effects Cell Survival - drug effects Cervical cancer Cervix Cytotoxicity Drug therapy Experiments FADD protein Fas-Associated Death Domain Protein - agonists Fas-Associated Death Domain Protein - genetics Fas-Associated Death Domain Protein - metabolism Female Flow cytometry Formulations Gene expression Gene Expression Regulation, Neoplastic Genetic aspects HeLa Cells Humans Inhibitory Concentration 50 Liliaceae - chemistry Medical research Membrane potential Membrane Potential, Mitochondrial - drug effects Mitochondria Mitochondria - drug effects Mitochondria - metabolism Mitochondria - pathology Molecular chains Molecular modelling Penicillin Pharmaceuticals Pharmacology Physiological aspects Rhizome - chemistry Rhizomes Saponins Saponins - isolation & purification Saponins - pharmacology Signal Transduction Tumor cells |
| title | Pennogenyl Saponins from Paris quadrifolia L. Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T20%3A05%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pennogenyl%20Saponins%20from%20Paris%20quadrifolia%20L.%20Induce%20Extrinsic%20and%20Intrinsic%20Pathway%20of%20Apoptosis%20in%20Human%20Cervical%20Cancer%20HeLa%20Cells&rft.jtitle=PloS%20one&rft.au=Stefanowicz-Hajduk,%20Justyna&rft.date=2015-08-21&rft.volume=10&rft.issue=8&rft.spage=e0135993&rft.epage=e0135993&rft.pages=e0135993-e0135993&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0135993&rft_dat=%3Cgale_plos_%3EA426228290%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1719000197&rft_id=info:pmid/26295969&rft_galeid=A426228290&rft_doaj_id=oai_doaj_org_article_cb8e0facb247405d92739f77f9e02c80&rfr_iscdi=true |