Repository logo
 
Publication

Prenylated chalcone 2 ccts as an antimitotic agent and enhances the chemosensitivity of tumor cells to paclitaxel

2016-08Journal article Open access
Simple item page
dc.contributor.authorFonseca, Joana
dc.contributor.authorMarques, Sandra
dc.contributor.authorSilva, PMA; Patrícia M.A. Silva
dc.contributor.authorBrandão, Pedro
dc.contributor.authorCidade, Honorina
dc.contributor.authorPinto, Madalena M.
dc.contributor.authorBousbaa, Hassan
dc.date.accessioned2017-04-07T15:56:17Z
dc.date.available2017-04-07T15:56:17Z
dc.date.issued2016-08
dc.description.abstractWe previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i) characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii) explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h) in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination.
dc.identifier.doi10.3390/molecules21080982
dc.identifier.issn1420-3049
dc.identifier.urihttp://hdl.handle.net/10400.1/9368
dc.language.isoeng
dc.peerreviewedyes
dc.relationTargeting p53 family proteins: on the route to new anticancer agents
dc.relationNavigating through marine-derived fungi: bioprospection and synthesis of bioactive secondary metabolites and analogues as chemotherapic agents
dc.relation.isbasedonWOS:000382334600021
dc.titlePrenylated chalcone 2 ccts as an antimitotic agent and enhances the chemosensitivity of tumor cells to paclitaxel
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTargeting p53 family proteins: on the route to new anticancer agents
oaire.awardTitleNavigating through marine-derived fungi: bioprospection and synthesis of bioactive secondary metabolites and analogues as chemotherapic agents
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F90744%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FDTP-FTO%2F1981%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FMAR-BIO%2F4694%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/COMPETE/PEst-C%2FMAR%2FLA0015%2F2013/PT
oaire.citation.endPage982
oaire.citation.issue8
oaire.citation.startPage982
oaire.citation.titleMolcules
oaire.citation.volume21
oaire.fundingStreamSFRH
oaire.fundingStream9471 - RIDTI
oaire.fundingStream9471 - RIDTI
oaire.fundingStreamCOMPETE
person.familyNameSilva
person.givenNamePatrícia
person.identifier1445798
person.identifier.ciencia-id4B19-7E26-A047
person.identifier.orcid0000-0002-0694-7321
person.identifier.scopus-author-id55855611900
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublicationc2baf55d-94d7-4d71-b9f6-307d37cd4685
relation.isAuthorOfPublication.latestForDiscoveryc2baf55d-94d7-4d71-b9f6-307d37cd4685
relation.isProjectOfPublicationeec7a7cf-4fd5-403f-b70a-cb2d401e1558
relation.isProjectOfPublication6a96c8bb-c0bf-4bed-a926-231f8eb18d6c
relation.isProjectOfPublicationf47cd75e-2a59-4302-8d9c-9e0e963235c9
relation.isProjectOfPublication54af5688-34c3-4241-8c3e-ae96076831ff
relation.isProjectOfPublication.latestForDiscovery6a96c8bb-c0bf-4bed-a926-231f8eb18d6c

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
9368.pdf
Size:
1 MB
Format:
Adobe Portable Document Format
Download

Collections

FCB2-Artigos (em revistas ou actas indexadas)