A novel epoxypropoxy flavonoid derivative and topoisomerase II inhibitor, MHY336, induces apoptosis in prostate cancer cells
Here, we reported the synthesis of a novel topoisomerase II inhibitor, MHY336, which that has strong topoisomerase-mediated anticancer activity but fewer side effects than other topoisomerase II inhibitors. The catalytic activity of MHY336 on the topoisomerase II enzyme was the same as that of the e...
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container_title | European journal of pharmacology |
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creator | Patra, Nabanita De, Umasankar Kang, Jin-Ah Kim, Ji Mim Ahn, Mee Young Lee, Jaewon Jung, Jee H. Chung, Hae Young Moon, Hyung Ryong Kim, Hyung Sik |
description | Here, we reported the synthesis of a novel topoisomerase II inhibitor, MHY336, which that has strong topoisomerase-mediated anticancer activity but fewer side effects than other topoisomerase II inhibitors. The catalytic activity of MHY336 on the topoisomerase II enzyme was the same as that of the etoposide. In a cell-free system, MHY336 exhibited a potent activity on scavenging of reactive oxygen species against 3-morpholinosydnonimine hydrochloride (SIN-1)-induced oxidative stress. An
in vitro cell-based assay demonstrated that MHY336 significantly inhibited the proliferation of three prostate cancer cell lines, LNCaP, PC-3, and DU145 cells. Notably, the cytotoxicity of MHY336 was more potent in LNCaP cells (IC
50
=
1.39
μM) than in DU145 (IC
50
=
2.94
μM) and PC3 cells (IC
50
=
3.72
μM). Furthermore, MHY336 treatment induced similar levels of cytotoxicity compared to doxorubicin treatment (IC
50
=
1.55
μM) in LNCap cells. Also, MHY336 significantly down-regulated topoisomerase II alpha expression and up-regulated p53 expression in LNCaP cells (wild-type p53), whereas it up-regulated the topoisomerase II alpha protein in both DU145 and PC3 cells (p53 mutated or deleted). MHY336 induced G2/M or S phase arrest in LNCaP cells through a well-documented topoisomerase II-dependent mechanism. Further studies using Annexin V-FITC binding assay, DAPI staining, and Western blot analyses illustrated that MHY336 markedly induced apoptotic cell death via the mitochondria-mediated intrinsic pathway in LNCaP cells. These results suggest that MHY336 is an attractive chemotherapeutic agent because of its topoisomerase II-mediated anti-tumour activity in human prostate cancer. |
doi_str_mv | 10.1016/j.ejphar.2011.02.015 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_860396462</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014299911002007</els_id><sourcerecordid>860396462</sourcerecordid><originalsourceid>FETCH-LOGICAL-c448t-6c2d90c6f0b90dc1739f9d5b3dc43249217f1b16a17d70a8df3417ff17bf85933</originalsourceid><addsrcrecordid>eNp9kctu1DAUhi0EotPCGyDwBsGiCb7FjjdIVVXoSEUsoAtWluML9SgTp3YmohIPj6MMsOvqSOd85_b_ALzCqMYI8w-72u3GO51qgjCuEakRbp6ADW6FrJDA5CnYIIRZRaSUJ-A05x1CqJGkeQ5OCKaCI0o34PcFHOLseujG-OthTHEJ0Pd6jkMMFlqXwqynMDuoBwunUg857l3S2cHtFobhLnRhiukcfrn-QSk_Lyl7MC5DPcZxijnkkoFlcp705KDRg3EJGtf3-QV45nWf3ctjPAO3n66-X15XN18_by8vbirDWDtV3BArkeEedRJZgwWVXtqmo9YwSpgkWHjcYa6xsALp1nrKSspj0fm2kZSegXfr3HLF_cHlSe1DXi7Qg4uHrNqiheSMk0K-f5TEjLeUtw0RBWUrasprOTmvxhT2Oj0ojNTikNqp1SG1OKQQUcWh0vb6uOHQ7Z391_TXkgK8PQI6G937VAQL-T_HEOdcLIPerJzXUemfqTC338qmptjMECbLMx9XwhVt5-CSyia4Ir8NyZlJ2Rgev_UPD426dA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1468368527</pqid></control><display><type>article</type><title>A novel epoxypropoxy flavonoid derivative and topoisomerase II inhibitor, MHY336, induces apoptosis in prostate cancer cells</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Patra, Nabanita ; De, Umasankar ; Kang, Jin-Ah ; Kim, Ji Mim ; Ahn, Mee Young ; Lee, Jaewon ; Jung, Jee H. ; Chung, Hae Young ; Moon, Hyung Ryong ; Kim, Hyung Sik</creator><creatorcontrib>Patra, Nabanita ; De, Umasankar ; Kang, Jin-Ah ; Kim, Ji Mim ; Ahn, Mee Young ; Lee, Jaewon ; Jung, Jee H. ; Chung, Hae Young ; Moon, Hyung Ryong ; Kim, Hyung Sik</creatorcontrib><description>Here, we reported the synthesis of a novel topoisomerase II inhibitor, MHY336, which that has strong topoisomerase-mediated anticancer activity but fewer side effects than other topoisomerase II inhibitors. The catalytic activity of MHY336 on the topoisomerase II enzyme was the same as that of the etoposide. In a cell-free system, MHY336 exhibited a potent activity on scavenging of reactive oxygen species against 3-morpholinosydnonimine hydrochloride (SIN-1)-induced oxidative stress. An
in vitro cell-based assay demonstrated that MHY336 significantly inhibited the proliferation of three prostate cancer cell lines, LNCaP, PC-3, and DU145 cells. Notably, the cytotoxicity of MHY336 was more potent in LNCaP cells (IC
50
=
1.39
μM) than in DU145 (IC
50
=
2.94
μM) and PC3 cells (IC
50
=
3.72
μM). Furthermore, MHY336 treatment induced similar levels of cytotoxicity compared to doxorubicin treatment (IC
50
=
1.55
μM) in LNCap cells. Also, MHY336 significantly down-regulated topoisomerase II alpha expression and up-regulated p53 expression in LNCaP cells (wild-type p53), whereas it up-regulated the topoisomerase II alpha protein in both DU145 and PC3 cells (p53 mutated or deleted). MHY336 induced G2/M or S phase arrest in LNCaP cells through a well-documented topoisomerase II-dependent mechanism. Further studies using Annexin V-FITC binding assay, DAPI staining, and Western blot analyses illustrated that MHY336 markedly induced apoptotic cell death via the mitochondria-mediated intrinsic pathway in LNCaP cells. These results suggest that MHY336 is an attractive chemotherapeutic agent because of its topoisomerase II-mediated anti-tumour activity in human prostate cancer.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2011.02.015</identifier><identifier>PMID: 21376033</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>adverse effects ; Annexins ; anticarcinogenic activity ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Biocatalysis - drug effects ; Biological and medical sciences ; catalytic activity ; Cell Cycle - drug effects ; cell free system ; Cell Line, Tumor ; Cell Proliferation - drug effects ; cytotoxicity ; DNA topoisomerase (ATP-hydrolysing) ; DNA Topoisomerases, Type II - metabolism ; Down-Regulation - drug effects ; doxorubicin ; flavonoids ; Flavonoids - chemical synthesis ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Free Radical Scavengers - chemical synthesis ; Free Radical Scavengers - chemistry ; Free Radical Scavengers - pharmacology ; Gynecology. Andrology. Obstetrics ; Humans ; interphase ; Male ; Male genital diseases ; Medical sciences ; MHY336 ; Molsidomine - analogs & derivatives ; Molsidomine - pharmacology ; Nephrology. Urinary tract diseases ; oxidative stress ; Oxidative Stress - drug effects ; p53 ; Pharmacology. Drug treatments ; Prostate cancer ; prostatic neoplasms ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; reactive oxygen species ; Reactive Oxygen Species - metabolism ; Topoisomerase II inhibitor ; Topoisomerase II Inhibitors - chemical synthesis ; Topoisomerase II Inhibitors - chemistry ; Topoisomerase II Inhibitors - pharmacology ; Tumor Suppressor Protein p53 - metabolism ; Tumors ; Tumors of the urinary system ; Up-Regulation - drug effects ; Urinary tract. Prostate gland ; Western blotting</subject><ispartof>European journal of pharmacology, 2011-05, Vol.658 (2), p.98-107</ispartof><rights>2011</rights><rights>2015 INIST-CNRS</rights><rights>Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-6c2d90c6f0b90dc1739f9d5b3dc43249217f1b16a17d70a8df3417ff17bf85933</citedby><cites>FETCH-LOGICAL-c448t-6c2d90c6f0b90dc1739f9d5b3dc43249217f1b16a17d70a8df3417ff17bf85933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2011.02.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24066675$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21376033$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Patra, Nabanita</creatorcontrib><creatorcontrib>De, Umasankar</creatorcontrib><creatorcontrib>Kang, Jin-Ah</creatorcontrib><creatorcontrib>Kim, Ji Mim</creatorcontrib><creatorcontrib>Ahn, Mee Young</creatorcontrib><creatorcontrib>Lee, Jaewon</creatorcontrib><creatorcontrib>Jung, Jee H.</creatorcontrib><creatorcontrib>Chung, Hae Young</creatorcontrib><creatorcontrib>Moon, Hyung Ryong</creatorcontrib><creatorcontrib>Kim, Hyung Sik</creatorcontrib><title>A novel epoxypropoxy flavonoid derivative and topoisomerase II inhibitor, MHY336, induces apoptosis in prostate cancer cells</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Here, we reported the synthesis of a novel topoisomerase II inhibitor, MHY336, which that has strong topoisomerase-mediated anticancer activity but fewer side effects than other topoisomerase II inhibitors. The catalytic activity of MHY336 on the topoisomerase II enzyme was the same as that of the etoposide. In a cell-free system, MHY336 exhibited a potent activity on scavenging of reactive oxygen species against 3-morpholinosydnonimine hydrochloride (SIN-1)-induced oxidative stress. An
in vitro cell-based assay demonstrated that MHY336 significantly inhibited the proliferation of three prostate cancer cell lines, LNCaP, PC-3, and DU145 cells. Notably, the cytotoxicity of MHY336 was more potent in LNCaP cells (IC
50
=
1.39
μM) than in DU145 (IC
50
=
2.94
μM) and PC3 cells (IC
50
=
3.72
μM). Furthermore, MHY336 treatment induced similar levels of cytotoxicity compared to doxorubicin treatment (IC
50
=
1.55
μM) in LNCap cells. Also, MHY336 significantly down-regulated topoisomerase II alpha expression and up-regulated p53 expression in LNCaP cells (wild-type p53), whereas it up-regulated the topoisomerase II alpha protein in both DU145 and PC3 cells (p53 mutated or deleted). MHY336 induced G2/M or S phase arrest in LNCaP cells through a well-documented topoisomerase II-dependent mechanism. Further studies using Annexin V-FITC binding assay, DAPI staining, and Western blot analyses illustrated that MHY336 markedly induced apoptotic cell death via the mitochondria-mediated intrinsic pathway in LNCaP cells. These results suggest that MHY336 is an attractive chemotherapeutic agent because of its topoisomerase II-mediated anti-tumour activity in human prostate cancer.</description><subject>adverse effects</subject><subject>Annexins</subject><subject>anticarcinogenic activity</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biocatalysis - drug effects</subject><subject>Biological and medical sciences</subject><subject>catalytic activity</subject><subject>Cell Cycle - drug effects</subject><subject>cell free system</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>cytotoxicity</subject><subject>DNA topoisomerase (ATP-hydrolysing)</subject><subject>DNA Topoisomerases, Type II - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>doxorubicin</subject><subject>flavonoids</subject><subject>Flavonoids - chemical synthesis</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Free Radical Scavengers - chemical synthesis</subject><subject>Free Radical Scavengers - chemistry</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>interphase</subject><subject>Male</subject><subject>Male genital diseases</subject><subject>Medical sciences</subject><subject>MHY336</subject><subject>Molsidomine - analogs & derivatives</subject><subject>Molsidomine - pharmacology</subject><subject>Nephrology. Urinary tract diseases</subject><subject>oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>p53</subject><subject>Pharmacology. Drug treatments</subject><subject>Prostate cancer</subject><subject>prostatic neoplasms</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Topoisomerase II inhibitor</subject><subject>Topoisomerase II Inhibitors - chemical synthesis</subject><subject>Topoisomerase II Inhibitors - chemistry</subject><subject>Topoisomerase II Inhibitors - pharmacology</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Up-Regulation - drug effects</subject><subject>Urinary tract. Prostate gland</subject><subject>Western blotting</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhi0EotPCGyDwBsGiCb7FjjdIVVXoSEUsoAtWluML9SgTp3YmohIPj6MMsOvqSOd85_b_ALzCqMYI8w-72u3GO51qgjCuEakRbp6ADW6FrJDA5CnYIIRZRaSUJ-A05x1CqJGkeQ5OCKaCI0o34PcFHOLseujG-OthTHEJ0Pd6jkMMFlqXwqynMDuoBwunUg857l3S2cHtFobhLnRhiukcfrn-QSk_Lyl7MC5DPcZxijnkkoFlcp705KDRg3EJGtf3-QV45nWf3ctjPAO3n66-X15XN18_by8vbirDWDtV3BArkeEedRJZgwWVXtqmo9YwSpgkWHjcYa6xsALp1nrKSspj0fm2kZSegXfr3HLF_cHlSe1DXi7Qg4uHrNqiheSMk0K-f5TEjLeUtw0RBWUrasprOTmvxhT2Oj0ojNTikNqp1SG1OKQQUcWh0vb6uOHQ7Z391_TXkgK8PQI6G937VAQL-T_HEOdcLIPerJzXUemfqTC338qmptjMECbLMx9XwhVt5-CSyia4Ir8NyZlJ2Rgev_UPD426dA</recordid><startdate>20110511</startdate><enddate>20110511</enddate><creator>Patra, Nabanita</creator><creator>De, Umasankar</creator><creator>Kang, Jin-Ah</creator><creator>Kim, Ji Mim</creator><creator>Ahn, Mee Young</creator><creator>Lee, Jaewon</creator><creator>Jung, Jee H.</creator><creator>Chung, Hae Young</creator><creator>Moon, Hyung Ryong</creator><creator>Kim, Hyung Sik</creator><general>Elsevier B.V</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20110511</creationdate><title>A novel epoxypropoxy flavonoid derivative and topoisomerase II inhibitor, MHY336, induces apoptosis in prostate cancer cells</title><author>Patra, Nabanita ; De, Umasankar ; Kang, Jin-Ah ; Kim, Ji Mim ; Ahn, Mee Young ; Lee, Jaewon ; Jung, Jee H. ; Chung, Hae Young ; Moon, Hyung Ryong ; Kim, Hyung Sik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-6c2d90c6f0b90dc1739f9d5b3dc43249217f1b16a17d70a8df3417ff17bf85933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>adverse effects</topic><topic>Annexins</topic><topic>anticarcinogenic activity</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biocatalysis - drug effects</topic><topic>Biological and medical sciences</topic><topic>catalytic activity</topic><topic>Cell Cycle - drug effects</topic><topic>cell free system</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>cytotoxicity</topic><topic>DNA topoisomerase (ATP-hydrolysing)</topic><topic>DNA Topoisomerases, Type II - metabolism</topic><topic>Down-Regulation - drug effects</topic><topic>doxorubicin</topic><topic>flavonoids</topic><topic>Flavonoids - chemical synthesis</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - pharmacology</topic><topic>Free Radical Scavengers - chemical synthesis</topic><topic>Free Radical Scavengers - chemistry</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>interphase</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>Medical sciences</topic><topic>MHY336</topic><topic>Molsidomine - analogs & derivatives</topic><topic>Molsidomine - pharmacology</topic><topic>Nephrology. Urinary tract diseases</topic><topic>oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>p53</topic><topic>Pharmacology. Drug treatments</topic><topic>Prostate cancer</topic><topic>prostatic neoplasms</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Topoisomerase II inhibitor</topic><topic>Topoisomerase II Inhibitors - chemical synthesis</topic><topic>Topoisomerase II Inhibitors - chemistry</topic><topic>Topoisomerase II Inhibitors - pharmacology</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Up-Regulation - drug effects</topic><topic>Urinary tract. Prostate gland</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Patra, Nabanita</creatorcontrib><creatorcontrib>De, Umasankar</creatorcontrib><creatorcontrib>Kang, Jin-Ah</creatorcontrib><creatorcontrib>Kim, Ji Mim</creatorcontrib><creatorcontrib>Ahn, Mee Young</creatorcontrib><creatorcontrib>Lee, Jaewon</creatorcontrib><creatorcontrib>Jung, Jee H.</creatorcontrib><creatorcontrib>Chung, Hae Young</creatorcontrib><creatorcontrib>Moon, Hyung Ryong</creatorcontrib><creatorcontrib>Kim, Hyung Sik</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>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Patra, Nabanita</au><au>De, Umasankar</au><au>Kang, Jin-Ah</au><au>Kim, Ji Mim</au><au>Ahn, Mee Young</au><au>Lee, Jaewon</au><au>Jung, Jee H.</au><au>Chung, Hae Young</au><au>Moon, Hyung Ryong</au><au>Kim, Hyung Sik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel epoxypropoxy flavonoid derivative and topoisomerase II inhibitor, MHY336, induces apoptosis in prostate cancer cells</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2011-05-11</date><risdate>2011</risdate><volume>658</volume><issue>2</issue><spage>98</spage><epage>107</epage><pages>98-107</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Here, we reported the synthesis of a novel topoisomerase II inhibitor, MHY336, which that has strong topoisomerase-mediated anticancer activity but fewer side effects than other topoisomerase II inhibitors. The catalytic activity of MHY336 on the topoisomerase II enzyme was the same as that of the etoposide. In a cell-free system, MHY336 exhibited a potent activity on scavenging of reactive oxygen species against 3-morpholinosydnonimine hydrochloride (SIN-1)-induced oxidative stress. An
in vitro cell-based assay demonstrated that MHY336 significantly inhibited the proliferation of three prostate cancer cell lines, LNCaP, PC-3, and DU145 cells. Notably, the cytotoxicity of MHY336 was more potent in LNCaP cells (IC
50
=
1.39
μM) than in DU145 (IC
50
=
2.94
μM) and PC3 cells (IC
50
=
3.72
μM). Furthermore, MHY336 treatment induced similar levels of cytotoxicity compared to doxorubicin treatment (IC
50
=
1.55
μM) in LNCap cells. Also, MHY336 significantly down-regulated topoisomerase II alpha expression and up-regulated p53 expression in LNCaP cells (wild-type p53), whereas it up-regulated the topoisomerase II alpha protein in both DU145 and PC3 cells (p53 mutated or deleted). MHY336 induced G2/M or S phase arrest in LNCaP cells through a well-documented topoisomerase II-dependent mechanism. Further studies using Annexin V-FITC binding assay, DAPI staining, and Western blot analyses illustrated that MHY336 markedly induced apoptotic cell death via the mitochondria-mediated intrinsic pathway in LNCaP cells. These results suggest that MHY336 is an attractive chemotherapeutic agent because of its topoisomerase II-mediated anti-tumour activity in human prostate cancer.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21376033</pmid><doi>10.1016/j.ejphar.2011.02.015</doi><tpages>10</tpages></addata></record> |
fulltext | fulltext |
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ispartof | European journal of pharmacology, 2011-05, Vol.658 (2), p.98-107 |
issn | 0014-2999 1879-0712 |
language | eng |
recordid | cdi_proquest_miscellaneous_860396462 |
source | MEDLINE; Elsevier ScienceDirect Journals Complete |
subjects | adverse effects Annexins anticarcinogenic activity Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Biocatalysis - drug effects Biological and medical sciences catalytic activity Cell Cycle - drug effects cell free system Cell Line, Tumor Cell Proliferation - drug effects cytotoxicity DNA topoisomerase (ATP-hydrolysing) DNA Topoisomerases, Type II - metabolism Down-Regulation - drug effects doxorubicin flavonoids Flavonoids - chemical synthesis Flavonoids - chemistry Flavonoids - pharmacology Free Radical Scavengers - chemical synthesis Free Radical Scavengers - chemistry Free Radical Scavengers - pharmacology Gynecology. Andrology. Obstetrics Humans interphase Male Male genital diseases Medical sciences MHY336 Molsidomine - analogs & derivatives Molsidomine - pharmacology Nephrology. Urinary tract diseases oxidative stress Oxidative Stress - drug effects p53 Pharmacology. Drug treatments Prostate cancer prostatic neoplasms Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology reactive oxygen species Reactive Oxygen Species - metabolism Topoisomerase II inhibitor Topoisomerase II Inhibitors - chemical synthesis Topoisomerase II Inhibitors - chemistry Topoisomerase II Inhibitors - pharmacology Tumor Suppressor Protein p53 - metabolism Tumors Tumors of the urinary system Up-Regulation - drug effects Urinary tract. Prostate gland Western blotting |
title | A novel epoxypropoxy flavonoid derivative and topoisomerase II inhibitor, MHY336, induces apoptosis in prostate cancer cells |
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