Antiepileptic drugs inhibit cell growth in the human breast cancer cell line MCF7

Olsen, Christel M.; Meussen‐Elholm, Elise T.M.; Røste, Line Sveberg; Taubøll, Erik

doi:10.1016/j.mce.2003.10.032

Cited by 54 publications

(34 citation statements)

References 44 publications

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“…Several other genes overexpressed in luminal A BCs code for therapeutic targets: ABAT (4-aminobutyrate aminotransferase), a target of the anti-epileptic drug valproic acid, which inhibits the growth of the MCF-7 luminal BC cell line, 81 and FNTB (farnesyl transferase B). Tipafarnib is a farnesyl-transferase inhibitor that enhances the tamoxifen inhibition of luminal MCF-7 growth 82 ; currently under evaluation in clinical trials, it might show greater activity in luminal A tumours.…”

Section: Extensive Transcriptional Differences Between Basal and Lumimentioning

confidence: 99%

How different are luminal A and basal breast cancers?

Bertucci

Finetti

Cervera

et al. 2008

Intl Journal of Cancer

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Heterogeneity of breast cancer makes its evolution difficult to predict, and its treatment far from being optimal. At least 5 main molecular subtypes exist. Two major subtypes are luminal A and basal subtypes, which have opposite features, notably survival. To characterize these 2 subtypes better, with the hope of better understanding their different biology and clinical outcome, we have profiled a series of 138 tumours (80 luminal A and 58 basal) using Affymetrix whole-genome DNA microarrays. We have identified 5,621 probe sets as differentially expressed between the 2 subtypes in our series. These differences were validated in 6 independent public series (more than 600 tumours) profiled using different DNA microarrays platforms. Analysis of functions and pathways related to these probe sets, and the extent of the observed differences, confirmed that the 2 subtypes represent very distinct entities. Genes associated with proliferation, cell cycle, cell motility, angiogenesis, and NFkB signalling were overexpressed in basal tumours. Genes involved in fatty acid metabolism, TGFB signalling, and oestrogen receptor (ER) signalling were overexpressed in luminal A samples. Half of the genes overexpressed in luminal tumours contained ER-binding sites. The number of differentially expressed genes was as high as the set of genes discriminating 2 cancers of different anatomical origin (breast and colon) or discriminating acute myeloid and lymphoid leukaemia. We provide a comprehensive list of genes/pathways that define potential diagnostic, prognostic and therapeutic targets for these 2 subtypes, which should be treated differently given the profound differences observed at the molecular level.

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Section: Extensive Transcriptional Differences Between Basal and Lumimentioning

confidence: 99%

How different are luminal A and basal breast cancers?

Bertucci

Finetti

Cervera

et al. 2008

Intl Journal of Cancer

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“…By modifying the epigenetic code, this novel class of therapeutic agents could suppress aberrant gene expression or activate gene transcription inhibiting tumor growth. 12 The anti-tumor properties of VPA have been observed in many cancer types, such as prostate cancer, 13 breast cancer, 14 glioma, 15 neuroblastoma 16 and in hematological malignancies. [17][18][19] Recently, our group showed that VPA at low pharmacological concentration could induce apoptosis of CLL B cells in vitro.…”

Section: Introductionmentioning

confidence: 99%

Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis

et al. 2009

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“…Altered expression of multiple genes, including the cyclindependent kinase inhibitor p21Cip1, glycogen synthase kinase-3h, and peroxisome proliferator-activated receptors, have been reported in cells exposed to valproic acid treatment (8 -10). Valproic acid has displayed potent in vitro and in vivo antitumor activities against neuroblastoma (11,12), glioma (13,14), leukemia (15,16), breast cancer (17) and prostate cancer (18), but effect of valproic acid in medulloblastoma and sPNET tumors remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC

Shu

et al. 2005

Molecular Cancer Therapeutics

183

133

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Valproic acid is a well-tolerated anticonvulsant that has been identified recently as a histone deacetylase inhibitor. To evaluate the antitumor efficacy and mechanisms of action of valproic acid in medulloblastoma and supratentorial primitive neuroectodermal tumor (sPNET), which are among the most common malignant brain tumors in children with poor prognosis, two medulloblastoma (DAOY and D283-MED) and one sPNET (PFSK) cell lines were treated with valproic acid and evaluated with a panel of in vitro and in vivo assays. Our results showed that valproic acid, at clinically safe concentrations (0.6 and 1 mmol/L), induced potent growth inhibition, cell cycle arrest, apoptosis, senescence, and differentiation and suppressed colony-forming efficiency and tumorigenicity in a time-and dose-dependent manner. The medulloblastoma cell lines were more responsive than the sPNET cell line and can be induced to irreversible suppression of proliferation and significantly reduced tumorigenicity by 0.6 and 1 mmol/L valproic acid. Daily i.p. injection of valproic acid (400 mg/kg) for 28 days significantly inhibited the in vivo growth of DAOY and D283-MED s.c. xenografts in severe combined immunodeficient mice. With Western hybridization and real-time reverse transcription-PCR, we further showed that the antitumor activities of valproic acid correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, and suppression of TP53, CDK4, and CMYC expression. In conclusion, valproic acid possesses potent in vitro and in vivo antimedulloblastoma activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, valproic acid may represent a novel therapeutic option in medulloblastoma treatment.

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Antiepileptic drugs inhibit cell growth in the human breast cancer cell line MCF7

Cited by 54 publications

References 44 publications

How different are luminal A and basal breast cancers?

How different are luminal A and basal breast cancers?

Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis

Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC

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