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Conference Paper: Evidence of a novel anti-apoptotic factor: Role of Id-1 in anticancer drug-induced apoptosis

TitleEvidence of a novel anti-apoptotic factor: Role of Id-1 in anticancer drug-induced apoptosis
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research
Citation
The 98th AACR Annual Meeting, Los Angeles, CA, 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, p. 5288 How to Cite?
AbstractId-1 (inhibitor of differentiation or DNA binding), a member of the basic helix-loop-helix (HLH) transcription factor family, is upregulated in many types of human cancer and its expression levels are correlated with poor treatment outcome and shorter survival. To study if Id-1 plays a positive role in protecting cancer cells from programmed cell death, we studied the role of Id-1 on five cancer cell lines derived from nasopharyngeal carcinoma (CNE1), cervical carcinoma (HeLa), breast cancer (MCF7), hepatocarcinoma (Huh7) and prostate cancer (PC3), all of which have been shown overexpression of Id-1 in clinical specimens. Nine commonly used anticancer drugs including two DNA damaging agents (cisplatin, mechlorethamine), one antibiotic (mitomycin C), two topoisomerase II inhibitors (doxorubicin, etoposide), one anti-metabolite (methotrexate), two microtubule disrupting agents (taxol, vincristine), and a green tea extract, epigallocatechin gallate (EGCG), were used to examine the association between Id-1 expression and the anticancer drug-induced apoptosis. After exposured to six types of anticancer agents, all of the cell lines showed a dose dependent downregulation of the Id-1 protein. In addition, the increased PARP cleavage was associated with increased TUNEL positive cells and decreased cell viability. The expression of cleaved PARP and percentage of TUNEL positive cells were suppressed significantly after treated with a caspase 9 inhibitor, Z-LEHD-FMK, though the expression of Id-1 was decreased after drug treatment, which suggested that apoptosis may be the result of Id-1 downregulation by anticancer drug treatment. To investigate if overexpression of Id-1 could protect cancer cells from apoptosis against all nine anticancer drugs, we treated two cell lines with high (CNE1 Id-1) and low (CNE1 pBabe) levels of Id-1 expression and found that overexpression of Id-1 was able to suppress PARP cleavage in response to all anticancer drugs examined. These results were reversed when we suppressed Id-1 expression in CNE1 cells through small RNA interference. We found that downregulation of Id-1 through small RNA technology in CNE1 cells led to increased sensitivity to all six types of chemotherapeutic drugs. In summary, our results demonstrate that Id-1 may be a general negative regulator of anticancer drug-induced apoptosis and suggest a novel therapeutic target in inducing chemosensitization in cancer cells. Our evidence also provides a possible underlying mechanism responsible for the positive role of Id-1 in the progression of human cancer.
DescriptionWinner of 2007 AACR-Avon Foundation Scholar-in-Training Grant
Persistent Identifierhttp://hdl.handle.net/10722/95384
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorWang, Xen_HK
dc.date.accessioned2010-09-25T16:00:35Z-
dc.date.available2010-09-25T16:00:35Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 98th AACR Annual Meeting, Los Angeles, CA, 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, p. 5288en_HK
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/95384-
dc.descriptionWinner of 2007 AACR-Avon Foundation Scholar-in-Training Grant-
dc.description.abstractId-1 (inhibitor of differentiation or DNA binding), a member of the basic helix-loop-helix (HLH) transcription factor family, is upregulated in many types of human cancer and its expression levels are correlated with poor treatment outcome and shorter survival. To study if Id-1 plays a positive role in protecting cancer cells from programmed cell death, we studied the role of Id-1 on five cancer cell lines derived from nasopharyngeal carcinoma (CNE1), cervical carcinoma (HeLa), breast cancer (MCF7), hepatocarcinoma (Huh7) and prostate cancer (PC3), all of which have been shown overexpression of Id-1 in clinical specimens. Nine commonly used anticancer drugs including two DNA damaging agents (cisplatin, mechlorethamine), one antibiotic (mitomycin C), two topoisomerase II inhibitors (doxorubicin, etoposide), one anti-metabolite (methotrexate), two microtubule disrupting agents (taxol, vincristine), and a green tea extract, epigallocatechin gallate (EGCG), were used to examine the association between Id-1 expression and the anticancer drug-induced apoptosis. After exposured to six types of anticancer agents, all of the cell lines showed a dose dependent downregulation of the Id-1 protein. In addition, the increased PARP cleavage was associated with increased TUNEL positive cells and decreased cell viability. The expression of cleaved PARP and percentage of TUNEL positive cells were suppressed significantly after treated with a caspase 9 inhibitor, Z-LEHD-FMK, though the expression of Id-1 was decreased after drug treatment, which suggested that apoptosis may be the result of Id-1 downregulation by anticancer drug treatment. To investigate if overexpression of Id-1 could protect cancer cells from apoptosis against all nine anticancer drugs, we treated two cell lines with high (CNE1 Id-1) and low (CNE1 pBabe) levels of Id-1 expression and found that overexpression of Id-1 was able to suppress PARP cleavage in response to all anticancer drugs examined. These results were reversed when we suppressed Id-1 expression in CNE1 cells through small RNA interference. We found that downregulation of Id-1 through small RNA technology in CNE1 cells led to increased sensitivity to all six types of chemotherapeutic drugs. In summary, our results demonstrate that Id-1 may be a general negative regulator of anticancer drug-induced apoptosis and suggest a novel therapeutic target in inducing chemosensitization in cancer cells. Our evidence also provides a possible underlying mechanism responsible for the positive role of Id-1 in the progression of human cancer.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_HK
dc.titleEvidence of a novel anti-apoptotic factor: Role of Id-1 in anticancer drug-induced apoptosisen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLing, MT: patling@HKUCC.hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.hkuros147353en_HK

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