Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3

Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver, occurs frequently in the setting of chronic liver injury. Although multiple therapeutic approaches are available, the prognosis of patients with HCC remains poor. Dioscin is a natural steroid saponin that presents...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Phytomedicine (Stuttgart) 2016-11, Vol.23 (12), p.1329-1336
Hauptverfasser: Zhang, Guangxian, Zeng, Xiancheng, Zhang, Ren, Liu, Juan, Zhang, Weici, Zhao, Yujun, Zhang, Xiaoyuan, Wu, Zhixue, Tan, Yuhui, Wu, Yingya, Du, Biaoyan
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1336
container_issue 12
container_start_page 1329
container_title Phytomedicine (Stuttgart)
container_volume 23
creator Zhang, Guangxian
Zeng, Xiancheng
Zhang, Ren
Liu, Juan
Zhang, Weici
Zhao, Yujun
Zhang, Xiaoyuan
Wu, Zhixue
Tan, Yuhui
Wu, Yingya
Du, Biaoyan
description Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver, occurs frequently in the setting of chronic liver injury. Although multiple therapeutic approaches are available, the prognosis of patients with HCC remains poor. Dioscin is a natural steroid saponin that presents in various plants. The anti-cancer and anti-fibrotic effects have been extensively reported. However, the effect of dioscin on HCC remains unclear. We aimed to investigate the anti-HCC properties of dioscin in vitro and in vivo. MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide) assay was used to analyze the growth inhibition activity of Dioscin in human cell lines, Bel-7402, HepG2, Lovo, and EAhy926. Antitumor activity through induction of apoptosis was evaluated by flow cytometry using Annexin-V and propidium iodide (PI) staining, laser scanning confocal microscopy (LSCM) analysis with Hochest33342 and PI labeling, and DNA fragmentation analysis. The expression of apoptosis-related proteins tumor protein p53 (TP53), BCL2-associated X protein (BAX), B-Cell CLL/Lymphoma 2 (BCL2) and Caspase 3 (CASP3) was measured by Western blot. Nude mice bearing Bel-7402 were administered intraperitoneally at different doses of dioscin and 5-FU (5-Fluorouracil) treatment was used as a control. Tumor volume and tumor weight of each mouse were then measured. We demonstrated that Dioscin inhibited proliferation of HCC cell lines in a dose-dependent manner. Dioscin also significantly induced morphological changes during death by apoptosis and increased DNA damage of Bel-7402 cells. Moreover, we demonstrated that Dioscin displayed anticancer activity via up-regulating expression of TP53, BAX and CASP3 protein, as well as down-regulating BCL2 in Bel-7402 cells. Notably, the in vivo anticancer activity of Dioscin was further assessed and achieved greater inhibition efficiency at the concentration increased to 24mg/kg/day than 5-FU at dose of 10mg/kg/day in nude mice bearing Bel-7402 cells. Dioscin inhibited tumor growth via inducing apoptosis, which was accompanied by altered expression of apoptotic pathway proteins, such as TP53, BAX, BCL2 and CASP3. Our findings indicate that further evaluation of dioscin as a novel therapeutic approach for HCC is warranted.
doi_str_mv 10.1016/j.phymed.2016.07.003
format Article
fullrecord <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1835527737</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A472679556</galeid><els_id>S0944711316301015</els_id><sourcerecordid>A472679556</sourcerecordid><originalsourceid>FETCH-LOGICAL-c537t-c951a418a280181b07e8ecb60a36f41bdba4900f86db5925b028da68f8cbbfde3</originalsourceid><addsrcrecordid>eNp9kl2L1DAUhoso7rj6D0QC3nhha9I2TXojjOMnDLjgCnsX8nHaydA23aRdmVt_uandvRAGCSTknOfN4Zy8SfKS4IxgUr07ZuPh1IPJ8njLMMswLh4lG1IRnuKa3jxONrguy5QRUlwkz0I4YkzKmuGnyUXOWEULmm-S3x-tC9oOKMzj6CEECOgAo5ychq6bO-mRlj4CrpdomnvnUevdr-mA1AnZwcwx1SI5unFywQYkB4M8tFE4WTcg16DrK1q8RR-2N3Hb7fO_hO5A3oFBu-2Pq-J58qSRXYAX9-dl8vPzp-vd13T__cu33XafalqwKdU1JbIkXOYcE04UZsBBqwrLompKooySZY1xwyujaJ1ThXNuZMUbrpVqDBSXyZv13dG72xnCJHobli7lAG4OgvCC0jiZgkX09Yq2sgNhh8ZNXuoFF9uS5RWrKa0ilZ6hWhjAy84N0NgY_ofPzvBxGeitPisoV4H2LgQPjRi97aU_CYLFYgJxFKsJxGICgZmIJoiyV_eNzmrJPYgefj0C71cA4rjvLHgRLQCDBmM96EkYZ_9f4Q-izMOr</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1835527737</pqid></control><display><type>article</type><title>Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Zhang, Guangxian ; Zeng, Xiancheng ; Zhang, Ren ; Liu, Juan ; Zhang, Weici ; Zhao, Yujun ; Zhang, Xiaoyuan ; Wu, Zhixue ; Tan, Yuhui ; Wu, Yingya ; Du, Biaoyan</creator><creatorcontrib>Zhang, Guangxian ; Zeng, Xiancheng ; Zhang, Ren ; Liu, Juan ; Zhang, Weici ; Zhao, Yujun ; Zhang, Xiaoyuan ; Wu, Zhixue ; Tan, Yuhui ; Wu, Yingya ; Du, Biaoyan</creatorcontrib><description>Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver, occurs frequently in the setting of chronic liver injury. Although multiple therapeutic approaches are available, the prognosis of patients with HCC remains poor. Dioscin is a natural steroid saponin that presents in various plants. The anti-cancer and anti-fibrotic effects have been extensively reported. However, the effect of dioscin on HCC remains unclear. We aimed to investigate the anti-HCC properties of dioscin in vitro and in vivo. MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide) assay was used to analyze the growth inhibition activity of Dioscin in human cell lines, Bel-7402, HepG2, Lovo, and EAhy926. Antitumor activity through induction of apoptosis was evaluated by flow cytometry using Annexin-V and propidium iodide (PI) staining, laser scanning confocal microscopy (LSCM) analysis with Hochest33342 and PI labeling, and DNA fragmentation analysis. The expression of apoptosis-related proteins tumor protein p53 (TP53), BCL2-associated X protein (BAX), B-Cell CLL/Lymphoma 2 (BCL2) and Caspase 3 (CASP3) was measured by Western blot. Nude mice bearing Bel-7402 were administered intraperitoneally at different doses of dioscin and 5-FU (5-Fluorouracil) treatment was used as a control. Tumor volume and tumor weight of each mouse were then measured. We demonstrated that Dioscin inhibited proliferation of HCC cell lines in a dose-dependent manner. Dioscin also significantly induced morphological changes during death by apoptosis and increased DNA damage of Bel-7402 cells. Moreover, we demonstrated that Dioscin displayed anticancer activity via up-regulating expression of TP53, BAX and CASP3 protein, as well as down-regulating BCL2 in Bel-7402 cells. Notably, the in vivo anticancer activity of Dioscin was further assessed and achieved greater inhibition efficiency at the concentration increased to 24mg/kg/day than 5-FU at dose of 10mg/kg/day in nude mice bearing Bel-7402 cells. Dioscin inhibited tumor growth via inducing apoptosis, which was accompanied by altered expression of apoptotic pathway proteins, such as TP53, BAX, BCL2 and CASP3. Our findings indicate that further evaluation of dioscin as a novel therapeutic approach for HCC is warranted.</description><identifier>ISSN: 0944-7113</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2016.07.003</identifier><identifier>PMID: 27765352</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Animals ; Antimetabolites, Antineoplastic - pharmacology ; Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis ; Apoptosis - drug effects ; bcl-2-Associated X Protein - biosynthesis ; bcl-2-Associated X Protein - genetics ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - pathology ; Care and treatment ; Caspase 3 - biosynthesis ; Caspase 3 - genetics ; Cell Line, Tumor ; Dioscin ; Diosgenin - analogs &amp; derivatives ; Diosgenin - pharmacology ; DNA damage ; DNA Fragmentation - drug effects ; Drug Screening Assays, Antitumor ; Fluorouracil - pharmacology ; Health aspects ; Hepatocellular carcinoma ; Hepatoma ; Humans ; Liver Neoplasms - drug therapy ; Liver Neoplasms - pathology ; Male ; Mice ; Mice, Nude ; Prevention ; Prognosis ; Proto-Oncogene Proteins c-bcl-2 - biosynthesis ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Saponins ; Tetrazolium Salts ; Thiazoles ; Tumor Suppressor Protein p53 - biosynthesis ; Tumor Suppressor Protein p53 - genetics</subject><ispartof>Phytomedicine (Stuttgart), 2016-11, Vol.23 (12), p.1329-1336</ispartof><rights>2016 Elsevier GmbH</rights><rights>Copyright © 2016 Elsevier GmbH. All rights reserved.</rights><rights>COPYRIGHT 2016 Urban &amp; Fischer Verlag</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-c951a418a280181b07e8ecb60a36f41bdba4900f86db5925b028da68f8cbbfde3</citedby><cites>FETCH-LOGICAL-c537t-c951a418a280181b07e8ecb60a36f41bdba4900f86db5925b028da68f8cbbfde3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.phymed.2016.07.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27765352$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Guangxian</creatorcontrib><creatorcontrib>Zeng, Xiancheng</creatorcontrib><creatorcontrib>Zhang, Ren</creatorcontrib><creatorcontrib>Liu, Juan</creatorcontrib><creatorcontrib>Zhang, Weici</creatorcontrib><creatorcontrib>Zhao, Yujun</creatorcontrib><creatorcontrib>Zhang, Xiaoyuan</creatorcontrib><creatorcontrib>Wu, Zhixue</creatorcontrib><creatorcontrib>Tan, Yuhui</creatorcontrib><creatorcontrib>Wu, Yingya</creatorcontrib><creatorcontrib>Du, Biaoyan</creatorcontrib><title>Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3</title><title>Phytomedicine (Stuttgart)</title><addtitle>Phytomedicine</addtitle><description>Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver, occurs frequently in the setting of chronic liver injury. Although multiple therapeutic approaches are available, the prognosis of patients with HCC remains poor. Dioscin is a natural steroid saponin that presents in various plants. The anti-cancer and anti-fibrotic effects have been extensively reported. However, the effect of dioscin on HCC remains unclear. We aimed to investigate the anti-HCC properties of dioscin in vitro and in vivo. MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide) assay was used to analyze the growth inhibition activity of Dioscin in human cell lines, Bel-7402, HepG2, Lovo, and EAhy926. Antitumor activity through induction of apoptosis was evaluated by flow cytometry using Annexin-V and propidium iodide (PI) staining, laser scanning confocal microscopy (LSCM) analysis with Hochest33342 and PI labeling, and DNA fragmentation analysis. The expression of apoptosis-related proteins tumor protein p53 (TP53), BCL2-associated X protein (BAX), B-Cell CLL/Lymphoma 2 (BCL2) and Caspase 3 (CASP3) was measured by Western blot. Nude mice bearing Bel-7402 were administered intraperitoneally at different doses of dioscin and 5-FU (5-Fluorouracil) treatment was used as a control. Tumor volume and tumor weight of each mouse were then measured. We demonstrated that Dioscin inhibited proliferation of HCC cell lines in a dose-dependent manner. Dioscin also significantly induced morphological changes during death by apoptosis and increased DNA damage of Bel-7402 cells. Moreover, we demonstrated that Dioscin displayed anticancer activity via up-regulating expression of TP53, BAX and CASP3 protein, as well as down-regulating BCL2 in Bel-7402 cells. Notably, the in vivo anticancer activity of Dioscin was further assessed and achieved greater inhibition efficiency at the concentration increased to 24mg/kg/day than 5-FU at dose of 10mg/kg/day in nude mice bearing Bel-7402 cells. Dioscin inhibited tumor growth via inducing apoptosis, which was accompanied by altered expression of apoptotic pathway proteins, such as TP53, BAX, BCL2 and CASP3. Our findings indicate that further evaluation of dioscin as a novel therapeutic approach for HCC is warranted.</description><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - pharmacology</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2-Associated X Protein - biosynthesis</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Care and treatment</subject><subject>Caspase 3 - biosynthesis</subject><subject>Caspase 3 - genetics</subject><subject>Cell Line, Tumor</subject><subject>Dioscin</subject><subject>Diosgenin - analogs &amp; derivatives</subject><subject>Diosgenin - pharmacology</subject><subject>DNA damage</subject><subject>DNA Fragmentation - drug effects</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Fluorouracil - pharmacology</subject><subject>Health aspects</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatoma</subject><subject>Humans</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Prevention</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-bcl-2 - biosynthesis</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Saponins</subject><subject>Tetrazolium Salts</subject><subject>Thiazoles</subject><subject>Tumor Suppressor Protein p53 - biosynthesis</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><issn>0944-7113</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kl2L1DAUhoso7rj6D0QC3nhha9I2TXojjOMnDLjgCnsX8nHaydA23aRdmVt_uandvRAGCSTknOfN4Zy8SfKS4IxgUr07ZuPh1IPJ8njLMMswLh4lG1IRnuKa3jxONrguy5QRUlwkz0I4YkzKmuGnyUXOWEULmm-S3x-tC9oOKMzj6CEECOgAo5ychq6bO-mRlj4CrpdomnvnUevdr-mA1AnZwcwx1SI5unFywQYkB4M8tFE4WTcg16DrK1q8RR-2N3Hb7fO_hO5A3oFBu-2Pq-J58qSRXYAX9-dl8vPzp-vd13T__cu33XafalqwKdU1JbIkXOYcE04UZsBBqwrLompKooySZY1xwyujaJ1ThXNuZMUbrpVqDBSXyZv13dG72xnCJHobli7lAG4OgvCC0jiZgkX09Yq2sgNhh8ZNXuoFF9uS5RWrKa0ilZ6hWhjAy84N0NgY_ofPzvBxGeitPisoV4H2LgQPjRi97aU_CYLFYgJxFKsJxGICgZmIJoiyV_eNzmrJPYgefj0C71cA4rjvLHgRLQCDBmM96EkYZ_9f4Q-izMOr</recordid><startdate>20161115</startdate><enddate>20161115</enddate><creator>Zhang, Guangxian</creator><creator>Zeng, Xiancheng</creator><creator>Zhang, Ren</creator><creator>Liu, Juan</creator><creator>Zhang, Weici</creator><creator>Zhao, Yujun</creator><creator>Zhang, Xiaoyuan</creator><creator>Wu, Zhixue</creator><creator>Tan, Yuhui</creator><creator>Wu, Yingya</creator><creator>Du, Biaoyan</creator><general>Elsevier GmbH</general><general>Urban &amp; Fischer Verlag</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>7X8</scope></search><sort><creationdate>20161115</creationdate><title>Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3</title><author>Zhang, Guangxian ; Zeng, Xiancheng ; Zhang, Ren ; Liu, Juan ; Zhang, Weici ; Zhao, Yujun ; Zhang, Xiaoyuan ; Wu, Zhixue ; Tan, Yuhui ; Wu, Yingya ; Du, Biaoyan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-c951a418a280181b07e8ecb60a36f41bdba4900f86db5925b028da68f8cbbfde3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antimetabolites, Antineoplastic - pharmacology</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>bcl-2-Associated X Protein - biosynthesis</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Care and treatment</topic><topic>Caspase 3 - biosynthesis</topic><topic>Caspase 3 - genetics</topic><topic>Cell Line, Tumor</topic><topic>Dioscin</topic><topic>Diosgenin - analogs &amp; derivatives</topic><topic>Diosgenin - pharmacology</topic><topic>DNA damage</topic><topic>DNA Fragmentation - drug effects</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Fluorouracil - pharmacology</topic><topic>Health aspects</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatoma</topic><topic>Humans</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Prevention</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins c-bcl-2 - biosynthesis</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Saponins</topic><topic>Tetrazolium Salts</topic><topic>Thiazoles</topic><topic>Tumor Suppressor Protein p53 - biosynthesis</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Guangxian</creatorcontrib><creatorcontrib>Zeng, Xiancheng</creatorcontrib><creatorcontrib>Zhang, Ren</creatorcontrib><creatorcontrib>Liu, Juan</creatorcontrib><creatorcontrib>Zhang, Weici</creatorcontrib><creatorcontrib>Zhao, Yujun</creatorcontrib><creatorcontrib>Zhang, Xiaoyuan</creatorcontrib><creatorcontrib>Wu, Zhixue</creatorcontrib><creatorcontrib>Tan, Yuhui</creatorcontrib><creatorcontrib>Wu, Yingya</creatorcontrib><creatorcontrib>Du, Biaoyan</creatorcontrib><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>Phytomedicine (Stuttgart)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Guangxian</au><au>Zeng, Xiancheng</au><au>Zhang, Ren</au><au>Liu, Juan</au><au>Zhang, Weici</au><au>Zhao, Yujun</au><au>Zhang, Xiaoyuan</au><au>Wu, Zhixue</au><au>Tan, Yuhui</au><au>Wu, Yingya</au><au>Du, Biaoyan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3</atitle><jtitle>Phytomedicine (Stuttgart)</jtitle><addtitle>Phytomedicine</addtitle><date>2016-11-15</date><risdate>2016</risdate><volume>23</volume><issue>12</issue><spage>1329</spage><epage>1336</epage><pages>1329-1336</pages><issn>0944-7113</issn><eissn>1618-095X</eissn><abstract>Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver, occurs frequently in the setting of chronic liver injury. Although multiple therapeutic approaches are available, the prognosis of patients with HCC remains poor. Dioscin is a natural steroid saponin that presents in various plants. The anti-cancer and anti-fibrotic effects have been extensively reported. However, the effect of dioscin on HCC remains unclear. We aimed to investigate the anti-HCC properties of dioscin in vitro and in vivo. MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide) assay was used to analyze the growth inhibition activity of Dioscin in human cell lines, Bel-7402, HepG2, Lovo, and EAhy926. Antitumor activity through induction of apoptosis was evaluated by flow cytometry using Annexin-V and propidium iodide (PI) staining, laser scanning confocal microscopy (LSCM) analysis with Hochest33342 and PI labeling, and DNA fragmentation analysis. The expression of apoptosis-related proteins tumor protein p53 (TP53), BCL2-associated X protein (BAX), B-Cell CLL/Lymphoma 2 (BCL2) and Caspase 3 (CASP3) was measured by Western blot. Nude mice bearing Bel-7402 were administered intraperitoneally at different doses of dioscin and 5-FU (5-Fluorouracil) treatment was used as a control. Tumor volume and tumor weight of each mouse were then measured. We demonstrated that Dioscin inhibited proliferation of HCC cell lines in a dose-dependent manner. Dioscin also significantly induced morphological changes during death by apoptosis and increased DNA damage of Bel-7402 cells. Moreover, we demonstrated that Dioscin displayed anticancer activity via up-regulating expression of TP53, BAX and CASP3 protein, as well as down-regulating BCL2 in Bel-7402 cells. Notably, the in vivo anticancer activity of Dioscin was further assessed and achieved greater inhibition efficiency at the concentration increased to 24mg/kg/day than 5-FU at dose of 10mg/kg/day in nude mice bearing Bel-7402 cells. Dioscin inhibited tumor growth via inducing apoptosis, which was accompanied by altered expression of apoptotic pathway proteins, such as TP53, BAX, BCL2 and CASP3. Our findings indicate that further evaluation of dioscin as a novel therapeutic approach for HCC is warranted.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>27765352</pmid><doi>10.1016/j.phymed.2016.07.003</doi><tpages>8</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0944-7113
ispartof Phytomedicine (Stuttgart), 2016-11, Vol.23 (12), p.1329-1336
issn 0944-7113
1618-095X
language eng
recordid cdi_proquest_miscellaneous_1835527737
source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Animals
Antimetabolites, Antineoplastic - pharmacology
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis
Apoptosis - drug effects
bcl-2-Associated X Protein - biosynthesis
bcl-2-Associated X Protein - genetics
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - pathology
Care and treatment
Caspase 3 - biosynthesis
Caspase 3 - genetics
Cell Line, Tumor
Dioscin
Diosgenin - analogs & derivatives
Diosgenin - pharmacology
DNA damage
DNA Fragmentation - drug effects
Drug Screening Assays, Antitumor
Fluorouracil - pharmacology
Health aspects
Hepatocellular carcinoma
Hepatoma
Humans
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
Male
Mice
Mice, Nude
Prevention
Prognosis
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Proto-Oncogene Proteins c-bcl-2 - genetics
Saponins
Tetrazolium Salts
Thiazoles
Tumor Suppressor Protein p53 - biosynthesis
Tumor Suppressor Protein p53 - genetics
title Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T20%3A49%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dioscin%20suppresses%20hepatocellular%20carcinoma%20tumor%20growth%20by%20inducing%20apoptosis%20and%20regulation%20of%20TP53,%20BAX,%20BCL2%20and%20cleaved%20CASP3&rft.jtitle=Phytomedicine%20(Stuttgart)&rft.au=Zhang,%20Guangxian&rft.date=2016-11-15&rft.volume=23&rft.issue=12&rft.spage=1329&rft.epage=1336&rft.pages=1329-1336&rft.issn=0944-7113&rft.eissn=1618-095X&rft_id=info:doi/10.1016/j.phymed.2016.07.003&rft_dat=%3Cgale_proqu%3EA472679556%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1835527737&rft_id=info:pmid/27765352&rft_galeid=A472679556&rft_els_id=S0944711316301015&rfr_iscdi=true