Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells
Cinnamaldehyde (Cin), cinnamic acid (Ca) and cinnamyl alcohol (Cal), major constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti-inflammatory, anticancer and other activities. In this study, our aim was to evaluate the antiproliferative activity of these compounds in human...
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| description | Cinnamaldehyde (Cin), cinnamic acid (Ca) and cinnamyl alcohol (Cal), major constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti-inflammatory, anticancer and other activities. In this study, our aim was to evaluate the antiproliferative activity of these compounds in human hepatoma Hep G2 cells and examine the effects of pifithrin-alpha (PFTα; a specific p53 inhibitor) on their apoptotic signaling transduction mechanism. The antiproliferative activity was measured by XTT assay. Expression of apoptosis-related proteins was detected by western blotting. Results showed that at a concentration of 30 μM, the order of antiproliferative activity in Hep G2 cells was Cin > Ca > Cal. Cin (IC50 9.76 ± 0.67 μM) demonstrated an antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC50 9.57 ± 0.61 μM). Further studies on apoptotic mechanisms of Cin showed that it downregulated the expression of Bcl-XL, upregulated CD95 (APO-1), p53 and Bax proteins, as well as cleaving the poly (ADP-ribose) polymerase (PARP) in a time-dependent pattern. PFTα pre-incubation significantly diminished the effect of Cin-induced apoptosis. It markedly upregulated the anti-apoptotic (Bcl-XL) expression and downregulated the pro-apoptotic (Bax) expression, as well as effectively blocking the CD95 (APO-1) and p53 expression, and PARP cleavage in Cin-treated cells. This study indicates that Cin was the most potent antiproliferative constituent of C. cassia, and its apoptotic mechanism in Hep G2 cells could be mediated through the p53 induction and CD95 (APO-1) signaling pathways. |
| doi_str_mv | 10.1093/ecam/nep220 |
| format | Article |
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In this study, our aim was to evaluate the antiproliferative activity of these compounds in human hepatoma Hep G2 cells and examine the effects of pifithrin-alpha (PFTα; a specific p53 inhibitor) on their apoptotic signaling transduction mechanism. The antiproliferative activity was measured by XTT assay. Expression of apoptosis-related proteins was detected by western blotting. Results showed that at a concentration of 30 μM, the order of antiproliferative activity in Hep G2 cells was Cin > Ca > Cal. Cin (IC50 9.76 ± 0.67 μM) demonstrated an antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC50 9.57 ± 0.61 μM). Further studies on apoptotic mechanisms of Cin showed that it downregulated the expression of Bcl-XL, upregulated CD95 (APO-1), p53 and Bax proteins, as well as cleaving the poly (ADP-ribose) polymerase (PARP) in a time-dependent pattern. PFTα pre-incubation significantly diminished the effect of Cin-induced apoptosis. It markedly upregulated the anti-apoptotic (Bcl-XL) expression and downregulated the pro-apoptotic (Bax) expression, as well as effectively blocking the CD95 (APO-1) and p53 expression, and PARP cleavage in Cin-treated cells. This study indicates that Cin was the most potent antiproliferative constituent of C. cassia, and its apoptotic mechanism in Hep G2 cells could be mediated through the p53 induction and CD95 (APO-1) signaling pathways.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1093/ecam/nep220</identifier><identifier>PMID: 20038571</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Puplishing Corporation</publisher><subject>5-Fluorouracil ; Adenosine diphosphate ; Alcoholic beverages ; Antioxidants ; Apoptosis ; BAX protein ; Bcl-x protein ; Cancer ; Cancer therapies ; CD95 antigen ; Cell cycle ; Cinnamaldehyde ; Cinnamic acid ; Cinnamomum cassia ; Constituents ; Deoxyribonucleic acid ; DNA ; Gene expression ; Hepatoma ; Inflammation ; Life sciences ; Medical research ; Original ; p53 Protein ; Penicillin ; Poly(ADP-ribose) polymerase ; Proteins ; Ribose ; Signal transduction ; Western blotting</subject><ispartof>Evidence-based complementary and alternative medicine, 2011-01, Vol.2011 (2011), p.1-6</ispartof><rights>Copyright © 2011 Lean-Teik Ng and Shu-Jing Wu.</rights><rights>Copyright © 2011 Lean-Teik Ng and Shu-Jing Wu. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2011 L.-T. Ng and S.-J. Wu. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-7b4a1568fd27f524e9702ba2463fc4d7170e9b5c05752b97909b5b7da386405e3</citedby><cites>FETCH-LOGICAL-c466t-7b4a1568fd27f524e9702ba2463fc4d7170e9b5c05752b97909b5b7da386405e3</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/PMC3135661/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135661/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20038571$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ng, Lean-Teik</creatorcontrib><creatorcontrib>Wu, Shu-Jing</creatorcontrib><title>Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>Cinnamaldehyde (Cin), cinnamic acid (Ca) and cinnamyl alcohol (Cal), major constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti-inflammatory, anticancer and other activities. In this study, our aim was to evaluate the antiproliferative activity of these compounds in human hepatoma Hep G2 cells and examine the effects of pifithrin-alpha (PFTα; a specific p53 inhibitor) on their apoptotic signaling transduction mechanism. The antiproliferative activity was measured by XTT assay. Expression of apoptosis-related proteins was detected by western blotting. Results showed that at a concentration of 30 μM, the order of antiproliferative activity in Hep G2 cells was Cin > Ca > Cal. Cin (IC50 9.76 ± 0.67 μM) demonstrated an antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC50 9.57 ± 0.61 μM). Further studies on apoptotic mechanisms of Cin showed that it downregulated the expression of Bcl-XL, upregulated CD95 (APO-1), p53 and Bax proteins, as well as cleaving the poly (ADP-ribose) polymerase (PARP) in a time-dependent pattern. PFTα pre-incubation significantly diminished the effect of Cin-induced apoptosis. It markedly upregulated the anti-apoptotic (Bcl-XL) expression and downregulated the pro-apoptotic (Bax) expression, as well as effectively blocking the CD95 (APO-1) and p53 expression, and PARP cleavage in Cin-treated cells. This study indicates that Cin was the most potent antiproliferative constituent of C. cassia, and its apoptotic mechanism in Hep G2 cells could be mediated through the p53 induction and CD95 (APO-1) signaling pathways.</description><subject>5-Fluorouracil</subject><subject>Adenosine diphosphate</subject><subject>Alcoholic beverages</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>BAX protein</subject><subject>Bcl-x protein</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>CD95 antigen</subject><subject>Cell cycle</subject><subject>Cinnamaldehyde</subject><subject>Cinnamic acid</subject><subject>Cinnamomum cassia</subject><subject>Constituents</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Gene expression</subject><subject>Hepatoma</subject><subject>Inflammation</subject><subject>Life sciences</subject><subject>Medical research</subject><subject>Original</subject><subject>p53 Protein</subject><subject>Penicillin</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Proteins</subject><subject>Ribose</subject><subject>Signal transduction</subject><subject>Western blotting</subject><issn>1741-427X</issn><issn>1741-4288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkV2L1TAQhoso7nr0ymsl4I0ox81H27Q3Qin7ISy44ArehTRNTmdpk5qku5yf4T_eLF0P6o1zMzPMw8vMvFn2muBPBNfsRCs5nVg9U4qfZMeE52Sb06p6eqj5j6PsRQg3GNOac_48O6IYs6rg5Dj71dgIs3cjGO1lhFuNGpUSxD1yBrVgrZzctExIyRBAotbZECEu2saApO3RqTFapTrRV2AgDh7sthnnQSJn0fWgwaNmdnN0ERT6BjsrR7A7dCXjcCf3AYFFF3pG5xS1ehzDy-yZkWPQrx7zJvt-dnrdXmwvv55_aZvLrcrLMm55l0tSlJXpKTcFzXXNMe0kzUtmVN5zwrGuu0Lhghe0q3mNU9fxXrKqzHGh2Sb7vOrOSzfpXqWDvBzF7GGSfi-cBPH3xMIgdu5WMMKKsiRJ4P2jgHc_Fx2imCCodIK02i1BEEx4-jepqoS--we9cYtPjwiC4hJXuGApNtnHlVLeheC1OSxDsHiwWjxYLVarE_32z_0P7G9vE_BhBQawvbyD_6i9WWGdEG3kAc55UbOc3QNgQsAP</recordid><startdate>20110101</startdate><enddate>20110101</enddate><creator>Ng, Lean-Teik</creator><creator>Wu, Shu-Jing</creator><general>Hindawi Puplishing Corporation</general><general>Hindawi Publishing Corporation</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110101</creationdate><title>Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells</title><author>Ng, Lean-Teik ; Wu, Shu-Jing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-7b4a1568fd27f524e9702ba2463fc4d7170e9b5c05752b97909b5b7da386405e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>5-Fluorouracil</topic><topic>Adenosine diphosphate</topic><topic>Alcoholic beverages</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>BAX protein</topic><topic>Bcl-x protein</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>CD95 antigen</topic><topic>Cell cycle</topic><topic>Cinnamaldehyde</topic><topic>Cinnamic acid</topic><topic>Cinnamomum cassia</topic><topic>Constituents</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Gene expression</topic><topic>Hepatoma</topic><topic>Inflammation</topic><topic>Life sciences</topic><topic>Medical research</topic><topic>Original</topic><topic>p53 Protein</topic><topic>Penicillin</topic><topic>Poly(ADP-ribose) polymerase</topic><topic>Proteins</topic><topic>Ribose</topic><topic>Signal transduction</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ng, Lean-Teik</creatorcontrib><creatorcontrib>Wu, Shu-Jing</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Evidence-based complementary and alternative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ng, Lean-Teik</au><au>Wu, Shu-Jing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells</atitle><jtitle>Evidence-based complementary and alternative medicine</jtitle><addtitle>Evid Based Complement Alternat Med</addtitle><date>2011-01-01</date><risdate>2011</risdate><volume>2011</volume><issue>2011</issue><spage>1</spage><epage>6</epage><pages>1-6</pages><issn>1741-427X</issn><eissn>1741-4288</eissn><abstract>Cinnamaldehyde (Cin), cinnamic acid (Ca) and cinnamyl alcohol (Cal), major constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti-inflammatory, anticancer and other activities. In this study, our aim was to evaluate the antiproliferative activity of these compounds in human hepatoma Hep G2 cells and examine the effects of pifithrin-alpha (PFTα; a specific p53 inhibitor) on their apoptotic signaling transduction mechanism. The antiproliferative activity was measured by XTT assay. Expression of apoptosis-related proteins was detected by western blotting. Results showed that at a concentration of 30 μM, the order of antiproliferative activity in Hep G2 cells was Cin > Ca > Cal. Cin (IC50 9.76 ± 0.67 μM) demonstrated an antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC50 9.57 ± 0.61 μM). Further studies on apoptotic mechanisms of Cin showed that it downregulated the expression of Bcl-XL, upregulated CD95 (APO-1), p53 and Bax proteins, as well as cleaving the poly (ADP-ribose) polymerase (PARP) in a time-dependent pattern. PFTα pre-incubation significantly diminished the effect of Cin-induced apoptosis. It markedly upregulated the anti-apoptotic (Bcl-XL) expression and downregulated the pro-apoptotic (Bax) expression, as well as effectively blocking the CD95 (APO-1) and p53 expression, and PARP cleavage in Cin-treated cells. This study indicates that Cin was the most potent antiproliferative constituent of C. cassia, and its apoptotic mechanism in Hep G2 cells could be mediated through the p53 induction and CD95 (APO-1) signaling pathways.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Puplishing Corporation</pub><pmid>20038571</pmid><doi>10.1093/ecam/nep220</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 5-Fluorouracil Adenosine diphosphate Alcoholic beverages Antioxidants Apoptosis BAX protein Bcl-x protein Cancer Cancer therapies CD95 antigen Cell cycle Cinnamaldehyde Cinnamic acid Cinnamomum cassia Constituents Deoxyribonucleic acid DNA Gene expression Hepatoma Inflammation Life sciences Medical research Original p53 Protein Penicillin Poly(ADP-ribose) polymerase Proteins Ribose Signal transduction Western blotting |
| title | Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells |
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