A cyano analogue of boswellic acid induces crosstalk between p53/PUMA/Bax and telomerase that stages the human papillomavirus type 18 positive HeLa cells to apoptotic death

The p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV) in over 90% of cervical cancers. HPV E6 protein promotes the degradation of p53 thereby inhibiting its stabilization and activation. This study demonstrates that treatment with a novel cyano derivative of 11-keto-β-boswellic...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:European journal of pharmacology 2011-06, Vol.660 (2-3), p.241-248
Hauptverfasser: Khan, Sheema, Chib, Renu, Shah, Bhahwal A., Wani, Z.A., Dhar, Niha, Mondhe, Dilip M., Lattoo, Surrinder, Jain, S.K., Taneja, Subhash C., Singh, Jaswant
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 248
container_issue 2-3
container_start_page 241
container_title European journal of pharmacology
container_volume 660
creator Khan, Sheema
Chib, Renu
Shah, Bhahwal A.
Wani, Z.A.
Dhar, Niha
Mondhe, Dilip M.
Lattoo, Surrinder
Jain, S.K.
Taneja, Subhash C.
Singh, Jaswant
description The p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV) in over 90% of cervical cancers. HPV E6 protein promotes the degradation of p53 thereby inhibiting its stabilization and activation. This study demonstrates that treatment with a novel cyano derivative of 11-keto-β-boswellic acid, i.e. butyl 2-cyano-3, 11-dioxours-1,12-dien-24-oate (BCDD) reduced the viral E6 mRNA expression and lead to the accumulation of transcriptionally active p53 in the nucleus of HPV18 HeLa cells following DNA damage. Western blot analysis showed that BCDD robustly up regulated time-dependent expression of p53/PUMA/p21 whereas it deprived cells essentially of p-AKT and NF-κB cell survival signalling cascade. BCDD appeared to gear up PUMA activation through p53 pathway and that both p53 and p21 translocated heavily into the nucleus. Simultaneously, it inhibited anti-apoptotic Bcl-2, augumented Drp-1 expression, disrupted mitochondrial functions causing the activation of proapoptotic proteins and caspases activation. Additionally, BCDD inhibited telomerase expression that's likely to result in a marked reduction of the tumorigenic potential of high-grade cervical cancers. Consequently BCDD caused apoptotic death in cervical cancer cells as evidenced by DNA fragmentation and PARP-cleavage. Further, BCDD did not affect the extrinsic signalling transduction pathway as depicted by its null effect on caspase-8. The in vivo anticancer activity of BCDD was investigated in Ehrlich Ascites carcinoma model where it exhibited tumor regression by 48% at 30mg/kg, i.p., in mice. These findings indicated that BCDD is a potential candidate that may be found useful in the management of cervical cancer.
doi_str_mv 10.1016/j.ejphar.2011.03.013
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_899137854</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014299911002846</els_id><sourcerecordid>867481169</sourcerecordid><originalsourceid>FETCH-LOGICAL-c423t-63deb5e5dd98541404aef9739cd30c143e219208a6beaa7f4354216e5b359dcd3</originalsourceid><addsrcrecordid>eNqFkU-P0zAQxSMEYsvCN0DIF8Sprf8m8QWprGAXqQgO7Nma2JOtSxqH2OnS78SHxN0WuMFpDvN7b57mFcVLRheMsnK5XeB22MC44JSxBRULysSjYsbqSs9pxfjjYkYpk3Outb4onsW4pZQqzdXT4oIzKakS5az4uSL2AH0g0EMX7iYkoSVNiPfYdd4SsN4R37vJYiR2DDEm6L6RBtM9Yk8GJZZfbj-tlu_gR3ZwJGEXdjhCRJI2kEjG77IybZBsph1kBQy-ywzs_TjlxWFAwmoyhOiT3yO5wTUQm4_nXQ41hCGFlIM4hLR5XjxpoYv44jwvi9sP779e3czXn68_Xq3Wcyu5SPNSOGwUKud0rSSTVAK2uhLaOkEtkwI505zWUDYIULVSKMlZiaoRSrsMXRZvTr7DGL5PGJPZ-XgMBT2GKZpaayaq7P1_sqxkzVipMylP5MMXR2zNMPodjAfDqDkWarbmVKg5FmqoMLnQLHt1PjA1O3R_RL8bzMDrMwDRQteO0Fsf_3KSU16qo9HbE4f5cXuPo4nWY2_R-RFtMi74fyf5Ba2mwi8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>867481169</pqid></control><display><type>article</type><title>A cyano analogue of boswellic acid induces crosstalk between p53/PUMA/Bax and telomerase that stages the human papillomavirus type 18 positive HeLa cells to apoptotic death</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Khan, Sheema ; Chib, Renu ; Shah, Bhahwal A. ; Wani, Z.A. ; Dhar, Niha ; Mondhe, Dilip M. ; Lattoo, Surrinder ; Jain, S.K. ; Taneja, Subhash C. ; Singh, Jaswant</creator><creatorcontrib>Khan, Sheema ; Chib, Renu ; Shah, Bhahwal A. ; Wani, Z.A. ; Dhar, Niha ; Mondhe, Dilip M. ; Lattoo, Surrinder ; Jain, S.K. ; Taneja, Subhash C. ; Singh, Jaswant</creatorcontrib><description>The p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV) in over 90% of cervical cancers. HPV E6 protein promotes the degradation of p53 thereby inhibiting its stabilization and activation. This study demonstrates that treatment with a novel cyano derivative of 11-keto-β-boswellic acid, i.e. butyl 2-cyano-3, 11-dioxours-1,12-dien-24-oate (BCDD) reduced the viral E6 mRNA expression and lead to the accumulation of transcriptionally active p53 in the nucleus of HPV18 HeLa cells following DNA damage. Western blot analysis showed that BCDD robustly up regulated time-dependent expression of p53/PUMA/p21 whereas it deprived cells essentially of p-AKT and NF-κB cell survival signalling cascade. BCDD appeared to gear up PUMA activation through p53 pathway and that both p53 and p21 translocated heavily into the nucleus. Simultaneously, it inhibited anti-apoptotic Bcl-2, augumented Drp-1 expression, disrupted mitochondrial functions causing the activation of proapoptotic proteins and caspases activation. Additionally, BCDD inhibited telomerase expression that's likely to result in a marked reduction of the tumorigenic potential of high-grade cervical cancers. Consequently BCDD caused apoptotic death in cervical cancer cells as evidenced by DNA fragmentation and PARP-cleavage. Further, BCDD did not affect the extrinsic signalling transduction pathway as depicted by its null effect on caspase-8. The in vivo anticancer activity of BCDD was investigated in Ehrlich Ascites carcinoma model where it exhibited tumor regression by 48% at 30mg/kg, i.p., in mice. These findings indicated that BCDD is a potential candidate that may be found useful in the management of cervical cancer.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2011.03.013</identifier><identifier>PMID: 21440536</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Apoptosis - drug effects ; Apoptosis Regulatory Proteins - metabolism ; bcl-2-Associated X Protein - metabolism ; Biological and medical sciences ; Carcinoma, Ehrlich Tumor - drug therapy ; Caspases - metabolism ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Cytotoxicity ; DNA Fragmentation - drug effects ; DNA-Binding Proteins - genetics ; Enzyme Activation - drug effects ; Gene Expression Regulation - drug effects ; Gene Expression Regulation, Neoplastic - drug effects ; HeLa Cells ; Human papilloma virus ; Human papillomavirus ; Human papillomavirus 18 ; Human papillomavirus 18 - physiology ; Humans ; Medical sciences ; Membrane Potential, Mitochondrial - drug effects ; Mice ; Mitochondria - drug effects ; Mitochondria - metabolism ; Nitriles - chemistry ; Nitriles - pharmacology ; Nitriles - therapeutic use ; Oncogene Proteins, Viral - genetics ; p53 ; Pharmacology. Drug treatments ; Polycyclic Compounds - chemistry ; Polycyclic Compounds - pharmacology ; Polycyclic Compounds - therapeutic use ; Proto-Oncogene Proteins - metabolism ; Resting Phase, Cell Cycle - drug effects ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction - drug effects ; Telomerase ; Telomerase - metabolism ; Triterpenes - chemistry ; Triterpenes - pharmacology ; Triterpenes - therapeutic use ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>European journal of pharmacology, 2011-06, Vol.660 (2-3), p.241-248</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-63deb5e5dd98541404aef9739cd30c143e219208a6beaa7f4354216e5b359dcd3</citedby><cites>FETCH-LOGICAL-c423t-63deb5e5dd98541404aef9739cd30c143e219208a6beaa7f4354216e5b359dcd3</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.2011.03.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=24202653$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21440536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khan, Sheema</creatorcontrib><creatorcontrib>Chib, Renu</creatorcontrib><creatorcontrib>Shah, Bhahwal A.</creatorcontrib><creatorcontrib>Wani, Z.A.</creatorcontrib><creatorcontrib>Dhar, Niha</creatorcontrib><creatorcontrib>Mondhe, Dilip M.</creatorcontrib><creatorcontrib>Lattoo, Surrinder</creatorcontrib><creatorcontrib>Jain, S.K.</creatorcontrib><creatorcontrib>Taneja, Subhash C.</creatorcontrib><creatorcontrib>Singh, Jaswant</creatorcontrib><title>A cyano analogue of boswellic acid induces crosstalk between p53/PUMA/Bax and telomerase that stages the human papillomavirus type 18 positive HeLa cells to apoptotic death</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>The p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV) in over 90% of cervical cancers. HPV E6 protein promotes the degradation of p53 thereby inhibiting its stabilization and activation. This study demonstrates that treatment with a novel cyano derivative of 11-keto-β-boswellic acid, i.e. butyl 2-cyano-3, 11-dioxours-1,12-dien-24-oate (BCDD) reduced the viral E6 mRNA expression and lead to the accumulation of transcriptionally active p53 in the nucleus of HPV18 HeLa cells following DNA damage. Western blot analysis showed that BCDD robustly up regulated time-dependent expression of p53/PUMA/p21 whereas it deprived cells essentially of p-AKT and NF-κB cell survival signalling cascade. BCDD appeared to gear up PUMA activation through p53 pathway and that both p53 and p21 translocated heavily into the nucleus. Simultaneously, it inhibited anti-apoptotic Bcl-2, augumented Drp-1 expression, disrupted mitochondrial functions causing the activation of proapoptotic proteins and caspases activation. Additionally, BCDD inhibited telomerase expression that's likely to result in a marked reduction of the tumorigenic potential of high-grade cervical cancers. Consequently BCDD caused apoptotic death in cervical cancer cells as evidenced by DNA fragmentation and PARP-cleavage. Further, BCDD did not affect the extrinsic signalling transduction pathway as depicted by its null effect on caspase-8. The in vivo anticancer activity of BCDD was investigated in Ehrlich Ascites carcinoma model where it exhibited tumor regression by 48% at 30mg/kg, i.p., in mice. These findings indicated that BCDD is a potential candidate that may be found useful in the management of cervical cancer.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Ehrlich Tumor - drug therapy</subject><subject>Caspases - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cytotoxicity</subject><subject>DNA Fragmentation - drug effects</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Enzyme Activation - drug effects</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>HeLa Cells</subject><subject>Human papilloma virus</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 18</subject><subject>Human papillomavirus 18 - physiology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mice</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Nitriles - chemistry</subject><subject>Nitriles - pharmacology</subject><subject>Nitriles - therapeutic use</subject><subject>Oncogene Proteins, Viral - genetics</subject><subject>p53</subject><subject>Pharmacology. Drug treatments</subject><subject>Polycyclic Compounds - chemistry</subject><subject>Polycyclic Compounds - pharmacology</subject><subject>Polycyclic Compounds - therapeutic use</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Resting Phase, Cell Cycle - drug effects</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Telomerase</subject><subject>Telomerase - metabolism</subject><subject>Triterpenes - chemistry</subject><subject>Triterpenes - pharmacology</subject><subject>Triterpenes - therapeutic use</subject><subject>Tumor Suppressor Protein p53 - metabolism</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>eNqFkU-P0zAQxSMEYsvCN0DIF8Sprf8m8QWprGAXqQgO7Nma2JOtSxqH2OnS78SHxN0WuMFpDvN7b57mFcVLRheMsnK5XeB22MC44JSxBRULysSjYsbqSs9pxfjjYkYpk3Outb4onsW4pZQqzdXT4oIzKakS5az4uSL2AH0g0EMX7iYkoSVNiPfYdd4SsN4R37vJYiR2DDEm6L6RBtM9Yk8GJZZfbj-tlu_gR3ZwJGEXdjhCRJI2kEjG77IybZBsph1kBQy-ywzs_TjlxWFAwmoyhOiT3yO5wTUQm4_nXQ41hCGFlIM4hLR5XjxpoYv44jwvi9sP779e3czXn68_Xq3Wcyu5SPNSOGwUKud0rSSTVAK2uhLaOkEtkwI505zWUDYIULVSKMlZiaoRSrsMXRZvTr7DGL5PGJPZ-XgMBT2GKZpaayaq7P1_sqxkzVipMylP5MMXR2zNMPodjAfDqDkWarbmVKg5FmqoMLnQLHt1PjA1O3R_RL8bzMDrMwDRQteO0Fsf_3KSU16qo9HbE4f5cXuPo4nWY2_R-RFtMi74fyf5Ba2mwi8</recordid><startdate>20110625</startdate><enddate>20110625</enddate><creator>Khan, Sheema</creator><creator>Chib, Renu</creator><creator>Shah, Bhahwal A.</creator><creator>Wani, Z.A.</creator><creator>Dhar, Niha</creator><creator>Mondhe, Dilip M.</creator><creator>Lattoo, Surrinder</creator><creator>Jain, S.K.</creator><creator>Taneja, Subhash C.</creator><creator>Singh, Jaswant</creator><general>Elsevier B.V</general><general>Elsevier</general><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><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20110625</creationdate><title>A cyano analogue of boswellic acid induces crosstalk between p53/PUMA/Bax and telomerase that stages the human papillomavirus type 18 positive HeLa cells to apoptotic death</title><author>Khan, Sheema ; Chib, Renu ; Shah, Bhahwal A. ; Wani, Z.A. ; Dhar, Niha ; Mondhe, Dilip M. ; Lattoo, Surrinder ; Jain, S.K. ; Taneja, Subhash C. ; Singh, Jaswant</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-63deb5e5dd98541404aef9739cd30c143e219208a6beaa7f4354216e5b359dcd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Ehrlich Tumor - drug therapy</topic><topic>Caspases - metabolism</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Cytotoxicity</topic><topic>DNA Fragmentation - drug effects</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Enzyme Activation - drug effects</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>HeLa Cells</topic><topic>Human papilloma virus</topic><topic>Human papillomavirus</topic><topic>Human papillomavirus 18</topic><topic>Human papillomavirus 18 - physiology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mice</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Nitriles - chemistry</topic><topic>Nitriles - pharmacology</topic><topic>Nitriles - therapeutic use</topic><topic>Oncogene Proteins, Viral - genetics</topic><topic>p53</topic><topic>Pharmacology. Drug treatments</topic><topic>Polycyclic Compounds - chemistry</topic><topic>Polycyclic Compounds - pharmacology</topic><topic>Polycyclic Compounds - therapeutic use</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Resting Phase, Cell Cycle - drug effects</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Telomerase</topic><topic>Telomerase - metabolism</topic><topic>Triterpenes - chemistry</topic><topic>Triterpenes - pharmacology</topic><topic>Triterpenes - therapeutic use</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khan, Sheema</creatorcontrib><creatorcontrib>Chib, Renu</creatorcontrib><creatorcontrib>Shah, Bhahwal A.</creatorcontrib><creatorcontrib>Wani, Z.A.</creatorcontrib><creatorcontrib>Dhar, Niha</creatorcontrib><creatorcontrib>Mondhe, Dilip M.</creatorcontrib><creatorcontrib>Lattoo, Surrinder</creatorcontrib><creatorcontrib>Jain, S.K.</creatorcontrib><creatorcontrib>Taneja, Subhash C.</creatorcontrib><creatorcontrib>Singh, Jaswant</creatorcontrib><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><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khan, Sheema</au><au>Chib, Renu</au><au>Shah, Bhahwal A.</au><au>Wani, Z.A.</au><au>Dhar, Niha</au><au>Mondhe, Dilip M.</au><au>Lattoo, Surrinder</au><au>Jain, S.K.</au><au>Taneja, Subhash C.</au><au>Singh, Jaswant</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A cyano analogue of boswellic acid induces crosstalk between p53/PUMA/Bax and telomerase that stages the human papillomavirus type 18 positive HeLa cells to apoptotic death</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2011-06-25</date><risdate>2011</risdate><volume>660</volume><issue>2-3</issue><spage>241</spage><epage>248</epage><pages>241-248</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>The p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV) in over 90% of cervical cancers. HPV E6 protein promotes the degradation of p53 thereby inhibiting its stabilization and activation. This study demonstrates that treatment with a novel cyano derivative of 11-keto-β-boswellic acid, i.e. butyl 2-cyano-3, 11-dioxours-1,12-dien-24-oate (BCDD) reduced the viral E6 mRNA expression and lead to the accumulation of transcriptionally active p53 in the nucleus of HPV18 HeLa cells following DNA damage. Western blot analysis showed that BCDD robustly up regulated time-dependent expression of p53/PUMA/p21 whereas it deprived cells essentially of p-AKT and NF-κB cell survival signalling cascade. BCDD appeared to gear up PUMA activation through p53 pathway and that both p53 and p21 translocated heavily into the nucleus. Simultaneously, it inhibited anti-apoptotic Bcl-2, augumented Drp-1 expression, disrupted mitochondrial functions causing the activation of proapoptotic proteins and caspases activation. Additionally, BCDD inhibited telomerase expression that's likely to result in a marked reduction of the tumorigenic potential of high-grade cervical cancers. Consequently BCDD caused apoptotic death in cervical cancer cells as evidenced by DNA fragmentation and PARP-cleavage. Further, BCDD did not affect the extrinsic signalling transduction pathway as depicted by its null effect on caspase-8. The in vivo anticancer activity of BCDD was investigated in Ehrlich Ascites carcinoma model where it exhibited tumor regression by 48% at 30mg/kg, i.p., in mice. These findings indicated that BCDD is a potential candidate that may be found useful in the management of cervical cancer.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21440536</pmid><doi>10.1016/j.ejphar.2011.03.013</doi><tpages>8</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0014-2999
ispartof European journal of pharmacology, 2011-06, Vol.660 (2-3), p.241-248
issn 0014-2999
1879-0712
language eng
recordid cdi_proquest_miscellaneous_899137854
source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis
Apoptosis - drug effects
Apoptosis Regulatory Proteins - metabolism
bcl-2-Associated X Protein - metabolism
Biological and medical sciences
Carcinoma, Ehrlich Tumor - drug therapy
Caspases - metabolism
Cell Proliferation - drug effects
Cell Survival - drug effects
Cytotoxicity
DNA Fragmentation - drug effects
DNA-Binding Proteins - genetics
Enzyme Activation - drug effects
Gene Expression Regulation - drug effects
Gene Expression Regulation, Neoplastic - drug effects
HeLa Cells
Human papilloma virus
Human papillomavirus
Human papillomavirus 18
Human papillomavirus 18 - physiology
Humans
Medical sciences
Membrane Potential, Mitochondrial - drug effects
Mice
Mitochondria - drug effects
Mitochondria - metabolism
Nitriles - chemistry
Nitriles - pharmacology
Nitriles - therapeutic use
Oncogene Proteins, Viral - genetics
p53
Pharmacology. Drug treatments
Polycyclic Compounds - chemistry
Polycyclic Compounds - pharmacology
Polycyclic Compounds - therapeutic use
Proto-Oncogene Proteins - metabolism
Resting Phase, Cell Cycle - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction - drug effects
Telomerase
Telomerase - metabolism
Triterpenes - chemistry
Triterpenes - pharmacology
Triterpenes - therapeutic use
Tumor Suppressor Protein p53 - metabolism
title A cyano analogue of boswellic acid induces crosstalk between p53/PUMA/Bax and telomerase that stages the human papillomavirus type 18 positive HeLa cells to apoptotic death
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%3A50%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20cyano%20analogue%20of%20boswellic%20acid%20induces%20crosstalk%20between%20p53/PUMA/Bax%20and%20telomerase%20that%20stages%20the%20human%20papillomavirus%20type%2018%20positive%20HeLa%20cells%20to%20apoptotic%20death&rft.jtitle=European%20journal%20of%20pharmacology&rft.au=Khan,%20Sheema&rft.date=2011-06-25&rft.volume=660&rft.issue=2-3&rft.spage=241&rft.epage=248&rft.pages=241-248&rft.issn=0014-2999&rft.eissn=1879-0712&rft.coden=EJPHAZ&rft_id=info:doi/10.1016/j.ejphar.2011.03.013&rft_dat=%3Cproquest_cross%3E867481169%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=867481169&rft_id=info:pmid/21440536&rft_els_id=S0014299911002846&rfr_iscdi=true