Induction of apoptosis by cinobufacini preparation through mitochondria- and Fas-mediated caspase-dependent pathways in human hepatocellular carcinoma cells
► Cinobufacini has apoptosis inducing effects on human hepatocellular carcinoma (HCC) cells. ► Cinobufacini induce apoptosis through both mitochondria- and Fas-mediated pathways. ► These findings provide an experimental evidence for cinobufacini treatment of HCC. Cinobufacini (Huachansu), an aqueous...
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description | ► Cinobufacini has apoptosis inducing effects on human hepatocellular carcinoma (HCC) cells. ► Cinobufacini induce apoptosis through both mitochondria- and Fas-mediated pathways. ► These findings provide an experimental evidence for cinobufacini treatment of HCC.
Cinobufacini (Huachansu), an aqueous extract from the skins of Bufo bufo gargarizans Cantor, is a well-known traditional Chinese medicine widely used in clinical cancer therapy in China. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. The aim of present study was to investigate possible apoptotic mechanisms induced by cinobufacini in HCC cell lines HepG2 and Bel-7402. We found that cinobufacini treatment resulted in a significant decrease in cell proliferation and induced apoptotic cell death with the increase of treatment time. It indicated that cinobufacini-induced apoptosis was associated with mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm), the increase of Bax/Bcl-2 ratio, cytochrome c release, caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) degradation. Additionally, cinobufacini also activated Fas-mediated apoptosis pathway obviously as evident by an increase in Fas expression, and caspase-8 and caspase-10 activation. Moreover, the BH3-only protein Bid was cleaved into a truncated Bid (tBid) after cinobufacini treatment. Taken together, these data suggested cinobufacini could induce apoptosis of HCC cells through mitochondria- and Fas-mediated caspase-dependent pathways with the increase of treatment time, which might provide an experimental evidence for cinobufacini treatment of HCC. |
doi_str_mv | 10.1016/j.fct.2011.10.040 |
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Cinobufacini (Huachansu), an aqueous extract from the skins of Bufo bufo gargarizans Cantor, is a well-known traditional Chinese medicine widely used in clinical cancer therapy in China. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. The aim of present study was to investigate possible apoptotic mechanisms induced by cinobufacini in HCC cell lines HepG2 and Bel-7402. We found that cinobufacini treatment resulted in a significant decrease in cell proliferation and induced apoptotic cell death with the increase of treatment time. It indicated that cinobufacini-induced apoptosis was associated with mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm), the increase of Bax/Bcl-2 ratio, cytochrome c release, caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) degradation. Additionally, cinobufacini also activated Fas-mediated apoptosis pathway obviously as evident by an increase in Fas expression, and caspase-8 and caspase-10 activation. Moreover, the BH3-only protein Bid was cleaved into a truncated Bid (tBid) after cinobufacini treatment. Taken together, these data suggested cinobufacini could induce apoptosis of HCC cells through mitochondria- and Fas-mediated caspase-dependent pathways with the increase of treatment time, which might provide an experimental evidence for cinobufacini treatment of HCC.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2011.10.040</identifier><identifier>PMID: 22019693</identifier><identifier>CODEN: FCTOD7</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Amphibian Venoms - chemistry ; Amphibian Venoms - pharmacology ; Animals ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Biological and medical sciences ; Bufo bufo ; Bufonidae - metabolism ; Caspase ; caspase-10 ; caspase-3 ; caspase-8 ; caspase-9 ; Caspases - metabolism ; cell proliferation ; Cinobufacini ; cytochrome c ; Fas Ligand Protein - metabolism ; Fas-mediated apoptosis pathway ; Gastroenterology. Liver. Pancreas. Abdomen ; HCC cells ; Hep G2 Cells ; hepatoma ; Humans ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Medicine, Chinese Traditional ; membrane potential ; Mitochondria - drug effects ; Mitochondria - enzymology ; Mitochondria-mediated apoptosis pathway ; mitochondrial membrane ; NAD ADP-ribosyltransferase ; Oriental traditional medicine ; Skin - chemistry ; Skin - metabolism ; therapeutics ; Toxicology ; Tumors</subject><ispartof>Food and chemical toxicology, 2012-02, Vol.50 (2), p.295-302</ispartof><rights>2011 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-9c13d92fc2ffe523236f79986232854e0e1017e9a097680283f0d7f2b61d984c3</citedby><cites>FETCH-LOGICAL-c472t-9c13d92fc2ffe523236f79986232854e0e1017e9a097680283f0d7f2b61d984c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.fct.2011.10.040$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25489258$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22019693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qi, Fanghua</creatorcontrib><creatorcontrib>Li, Anyuan</creatorcontrib><creatorcontrib>Inagaki, Yoshinori</creatorcontrib><creatorcontrib>Xu, Huanli</creatorcontrib><creatorcontrib>Wang, Dongliang</creatorcontrib><creatorcontrib>Cui, Xiaoyan</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Kokudo, Norihiro</creatorcontrib><creatorcontrib>Du, Guanhua</creatorcontrib><creatorcontrib>Tang, Wei</creatorcontrib><title>Induction of apoptosis by cinobufacini preparation through mitochondria- and Fas-mediated caspase-dependent pathways in human hepatocellular carcinoma cells</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>► Cinobufacini has apoptosis inducing effects on human hepatocellular carcinoma (HCC) cells. ► Cinobufacini induce apoptosis through both mitochondria- and Fas-mediated pathways. ► These findings provide an experimental evidence for cinobufacini treatment of HCC.
Cinobufacini (Huachansu), an aqueous extract from the skins of Bufo bufo gargarizans Cantor, is a well-known traditional Chinese medicine widely used in clinical cancer therapy in China. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. The aim of present study was to investigate possible apoptotic mechanisms induced by cinobufacini in HCC cell lines HepG2 and Bel-7402. We found that cinobufacini treatment resulted in a significant decrease in cell proliferation and induced apoptotic cell death with the increase of treatment time. It indicated that cinobufacini-induced apoptosis was associated with mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm), the increase of Bax/Bcl-2 ratio, cytochrome c release, caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) degradation. Additionally, cinobufacini also activated Fas-mediated apoptosis pathway obviously as evident by an increase in Fas expression, and caspase-8 and caspase-10 activation. Moreover, the BH3-only protein Bid was cleaved into a truncated Bid (tBid) after cinobufacini treatment. Taken together, these data suggested cinobufacini could induce apoptosis of HCC cells through mitochondria- and Fas-mediated caspase-dependent pathways with the increase of treatment time, which might provide an experimental evidence for cinobufacini treatment of HCC.</description><subject>Amphibian Venoms - chemistry</subject><subject>Amphibian Venoms - pharmacology</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Bufo bufo</subject><subject>Bufonidae - metabolism</subject><subject>Caspase</subject><subject>caspase-10</subject><subject>caspase-3</subject><subject>caspase-8</subject><subject>caspase-9</subject><subject>Caspases - metabolism</subject><subject>cell proliferation</subject><subject>Cinobufacini</subject><subject>cytochrome c</subject><subject>Fas Ligand Protein - metabolism</subject><subject>Fas-mediated apoptosis pathway</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>HCC cells</subject><subject>Hep G2 Cells</subject><subject>hepatoma</subject><subject>Humans</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Medicine, Chinese Traditional</subject><subject>membrane potential</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - enzymology</subject><subject>Mitochondria-mediated apoptosis pathway</subject><subject>mitochondrial membrane</subject><subject>NAD ADP-ribosyltransferase</subject><subject>Oriental traditional medicine</subject><subject>Skin - chemistry</subject><subject>Skin - metabolism</subject><subject>therapeutics</subject><subject>Toxicology</subject><subject>Tumors</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotuFH8AFfEE9ZbGdD8fihCoKlSpxgJ6jWX80XiV2sJOi_S_8WCbsAjcuHnv0zDvjeQl5xdmOM968O-ycnneCcY7vHavYE7LhrSyLpqz5U7JhQrZFo3h9QS5zPjDGJJfNc3IhsEY1qtyQn7fBLHr2MdDoKExxmmP2me6PVPsQ94sDjJ5OyU6Q4Dc49ykuDz0d_Rx1H4NJHgoKwdAbyMVojYfZGqohT5BtYexkg7FhphPM_Q84ZuoD7ZcR8ERVFLHDsAyQsCStXUegayq_IM8cDNm-PMctub_5-O36c3H35dPt9Ye7QldSzIXSvDRKOC2cs7UoRdk4qVTb4LWtK8ssbktaBUzJpmWiLR0z0ol9w41qK11uydVJd0rx-2Lz3I0-rxNAsHHJneJtLetStUjyE6lTzDlZ103Jj5COHWfd6kl36NCTbvVkTaEnWPP6rL7scTl_K_6YgMDbMwBZw-ASBO3zP66uWiXqtfmbE-cgdvCQkLn_iiI1w-9xicZvyfsTYXFbj96mLmtvg0ZLksWxTPT_GfQXa0a1sQ</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Qi, Fanghua</creator><creator>Li, Anyuan</creator><creator>Inagaki, Yoshinori</creator><creator>Xu, Huanli</creator><creator>Wang, Dongliang</creator><creator>Cui, Xiaoyan</creator><creator>Zhang, Li</creator><creator>Kokudo, Norihiro</creator><creator>Du, Guanhua</creator><creator>Tang, Wei</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20120201</creationdate><title>Induction of apoptosis by cinobufacini preparation through mitochondria- and Fas-mediated caspase-dependent pathways in human hepatocellular carcinoma cells</title><author>Qi, Fanghua ; Li, Anyuan ; Inagaki, Yoshinori ; Xu, Huanli ; Wang, Dongliang ; Cui, Xiaoyan ; Zhang, Li ; Kokudo, Norihiro ; Du, Guanhua ; Tang, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-9c13d92fc2ffe523236f79986232854e0e1017e9a097680283f0d7f2b61d984c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Amphibian Venoms - chemistry</topic><topic>Amphibian Venoms - pharmacology</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Bufo bufo</topic><topic>Bufonidae - metabolism</topic><topic>Caspase</topic><topic>caspase-10</topic><topic>caspase-3</topic><topic>caspase-8</topic><topic>caspase-9</topic><topic>Caspases - metabolism</topic><topic>cell proliferation</topic><topic>Cinobufacini</topic><topic>cytochrome c</topic><topic>Fas Ligand Protein - metabolism</topic><topic>Fas-mediated apoptosis pathway</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>HCC cells</topic><topic>Hep G2 Cells</topic><topic>hepatoma</topic><topic>Humans</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Medicine, Chinese Traditional</topic><topic>membrane potential</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - enzymology</topic><topic>Mitochondria-mediated apoptosis pathway</topic><topic>mitochondrial membrane</topic><topic>NAD ADP-ribosyltransferase</topic><topic>Oriental traditional medicine</topic><topic>Skin - chemistry</topic><topic>Skin - metabolism</topic><topic>therapeutics</topic><topic>Toxicology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qi, Fanghua</creatorcontrib><creatorcontrib>Li, Anyuan</creatorcontrib><creatorcontrib>Inagaki, Yoshinori</creatorcontrib><creatorcontrib>Xu, Huanli</creatorcontrib><creatorcontrib>Wang, Dongliang</creatorcontrib><creatorcontrib>Cui, Xiaoyan</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Kokudo, Norihiro</creatorcontrib><creatorcontrib>Du, Guanhua</creatorcontrib><creatorcontrib>Tang, Wei</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Food and chemical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qi, Fanghua</au><au>Li, Anyuan</au><au>Inagaki, Yoshinori</au><au>Xu, Huanli</au><au>Wang, Dongliang</au><au>Cui, Xiaoyan</au><au>Zhang, Li</au><au>Kokudo, Norihiro</au><au>Du, Guanhua</au><au>Tang, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of apoptosis by cinobufacini preparation through mitochondria- and Fas-mediated caspase-dependent pathways in human hepatocellular carcinoma cells</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>50</volume><issue>2</issue><spage>295</spage><epage>302</epage><pages>295-302</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><coden>FCTOD7</coden><abstract>► Cinobufacini has apoptosis inducing effects on human hepatocellular carcinoma (HCC) cells. ► Cinobufacini induce apoptosis through both mitochondria- and Fas-mediated pathways. ► These findings provide an experimental evidence for cinobufacini treatment of HCC.
Cinobufacini (Huachansu), an aqueous extract from the skins of Bufo bufo gargarizans Cantor, is a well-known traditional Chinese medicine widely used in clinical cancer therapy in China. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. The aim of present study was to investigate possible apoptotic mechanisms induced by cinobufacini in HCC cell lines HepG2 and Bel-7402. We found that cinobufacini treatment resulted in a significant decrease in cell proliferation and induced apoptotic cell death with the increase of treatment time. It indicated that cinobufacini-induced apoptosis was associated with mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm), the increase of Bax/Bcl-2 ratio, cytochrome c release, caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) degradation. Additionally, cinobufacini also activated Fas-mediated apoptosis pathway obviously as evident by an increase in Fas expression, and caspase-8 and caspase-10 activation. Moreover, the BH3-only protein Bid was cleaved into a truncated Bid (tBid) after cinobufacini treatment. Taken together, these data suggested cinobufacini could induce apoptosis of HCC cells through mitochondria- and Fas-mediated caspase-dependent pathways with the increase of treatment time, which might provide an experimental evidence for cinobufacini treatment of HCC.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>22019693</pmid><doi>10.1016/j.fct.2011.10.040</doi><tpages>8</tpages></addata></record> |
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subjects | Amphibian Venoms - chemistry Amphibian Venoms - pharmacology Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Biological and medical sciences Bufo bufo Bufonidae - metabolism Caspase caspase-10 caspase-3 caspase-8 caspase-9 Caspases - metabolism cell proliferation Cinobufacini cytochrome c Fas Ligand Protein - metabolism Fas-mediated apoptosis pathway Gastroenterology. Liver. Pancreas. Abdomen HCC cells Hep G2 Cells hepatoma Humans Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Medicine, Chinese Traditional membrane potential Mitochondria - drug effects Mitochondria - enzymology Mitochondria-mediated apoptosis pathway mitochondrial membrane NAD ADP-ribosyltransferase Oriental traditional medicine Skin - chemistry Skin - metabolism therapeutics Toxicology Tumors |
title | Induction of apoptosis by cinobufacini preparation through mitochondria- and Fas-mediated caspase-dependent pathways in human hepatocellular carcinoma cells |
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