Enhanced gene transfer and cell death following p53 gene transfer using photochemical internalisation of glucosylated PEI‐DNA complexes

Ndoye, Alioune; Merlin, Jean Louis; Leroux, Agnès; Dolivet, Gilles; Erbacher, Patrick; Behr, Jean Paul; Berg, Kristian; Guillemin, François

doi:10.1002/jgm.573

Cited by 49 publications

(30 citation statements)

References 45 publications

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“…Introduction of p53 expression resulted in a significant increase in growth inhibition and apoptosis induction, thus confirming the well-established essential function of P53 as mediator of cell growth and apoptosis control already reported in the literature with p53 gene transfer in head and neck, and pancreatic cancer cell lines. 26,27 These results are in agreement with a previous study, 11 which demonstrated that, in PTEN-deficient cells, p53 regulates cell survival by transcriptional downregulation of PIK3-CA (encoding p110 catalytic subunit of PI3K) independently of PTEN. Conversely, in pten intact cells, induction of p53 downregulates PIK3CA and increases PTEN protein expression 12 through a p53 response element located into PIK3CA promoter.…”

Section: Discussionsupporting

confidence: 92%

P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab

Bouali

Ramacci

et al. 2009

Cancer Gene Ther

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Cetuximab (Erbitux) is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody whose activity is related to the inhibition of EGFR downstream signaling pathways. P53 and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) have been reported to control the functionality of PI3K/AKT signaling. In this study we evaluated whether reintroducing P53 using non-viral gene transfer enhances PTEN-mediated inhibition of PI3K/AKT signaling by cetuximab in PC3 prostate adenocarcinoma cell line bearing p53 and pten mutations. Signaling phosphoproteins expression was analyzed using Bio-Plex phosphoprotein array and western blot. Apoptosis induction was evaluated from BAX expression, caspase-3 activation and DNA fragmentation analyses. The results presented show that p53 and pten gene transfer additionally mediated cell growth inhibition and apoptosis induction by restoral of signaling functionality, which enabled the control of PI3K/AKT and MAPKinase signaling pathways by cetuximab in PC3 cells. These results highlight the interest of the analysis of signaling phosphoproteins expression as molecular predictive markers for response to cetuximab and show that p53 and pten mutations could be key determinants of cell response to cetuximab through the functional impact of these mutations on cell signaling.

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Section: Discussionsupporting

confidence: 92%

P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab

Bouali

Ramacci

et al. 2009

Cancer Gene Ther

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“…PCI resulted in increased p53 mRNA expression by 2.3-fold in PANC3 cells, compared to PEI alone (Ndoye et al, 2004). PCI also increased apoptosis in both lines to levels similar to those achieved with chemotherapy.…”

mentioning

confidence: 56%

“…The principle of PCI is to localise the photosensitiser together with the drug or gene of choice in endocytic vesicles within target cells, with the photosensitiser specifically localising to the vesicular membrane (Høgset et al, 2004;Ndoye et al, 2004;Dietze et al, 2005). Irradiation of cells with light of a specific wavelength will excite the photosensitiser to produce reactive oxygen species which subsequently rapture the membranes (Figure 1), resulting in drugs release.…”

mentioning

confidence: 99%

“…Irradiation of cells with light of a specific wavelength will excite the photosensitiser to produce reactive oxygen species which subsequently rapture the membranes (Figure 1), resulting in drugs release. (Høgset et al, 2004;Ndoye et al, 2004;Dietze et al, 2005). Consequently, PCI enables a more efficient delivery of drug to their intracellular targets (Berg et al, 1999;Selbo et al, 2001;Høgset et al, 2004).…”

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confidence: 99%

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Photochemical internalisation of chemotherapy potentiates killing of multidrug-resistant breast and bladder cancer cells

et al. 2007

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Multidrug resistance (MDR) is the major confounding factor in adjuvant solid tumour chemotherapy. Increasing intracellular amounts of chemotherapeutics to circumvent MDR may be achieved by a novel delivery method, photochemical internalisation (PCI). PCI consists of the co-administration of drug and photosensitiser; upon light activation the latter induces intracellular release of organellebound drug. We investigated whether co-administration of hypericin (photosensitiser) with mitoxantrone (MTZ, chemotherapeutic) plus illumination potentiates cytotoxicity in MDR cancer cells. We mapped the extent of intracellular co-localisation of drug/ photosensitiser. We determined whether PCI altered drug-excreting efflux pump P-glycoprotein (Pgp) expression or function in MDR cells. Bladder and breast cancer cells and their Pgp-overexpressing MDR subclones (MGHU1, MGHU1/R, MCF-7, MCF-7/R) were given hypericin/MTZ combinations, with/without blue-light illumination. Pilot experiments determined appropriate sublethal doses for each. Viability was determined by the 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazolium bromide assay. Intracellular localisation was mapped by confocal microscopy. Pgp expression was detected by immunofluorescence and Pgp function investigated by Rhodamine123 efflux on confocal microscopy. MTZ alone (0.1 -0.2 mg ml À1 ) killed up to 89% of drug-sensitive cells; MDR cells exhibited less cytotoxicity (6 -28%). Hypericin (0.1 -0.2 mM) effects were similar for all cells; light illumination caused none or minimal toxicity. In combination, MTZ /hypericin plus illumination, potentiated MDR cell killing, vs hypericin or MTZ alone. (MGHU1/R: 38.65 and 36.63% increase, Po0.05; MCF-7/R: 80.2 and 46.1% increase, Po0.001). Illumination of combined MTZ/hypericin increased killing by 28.15% (Po0.05 MGHU1/R) compared to dark controls. Intracytoplasmic vesicular co-localisation of MTZ/hypericin was evident before illumination and at serial times post-illumination. MTZ was always found in sensitive cell nuclei, but not in dark resistant cell nuclei. In illuminated resistant cells there was some mobilisation of MTZ into the nucleus. Pgp expression remained unchanged, regardless of drug exposure. Pgp efflux was blocked by the Pgp inhibitor verapamil (positive control) but not impeded by hypericin. The increased killing of MDR cancer cells demonstrated is consistent with PCI. PCI is a promising technique for enhancing treatment efficacy.

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“…Each of the envisaged applications has is own particular requirements and therefore a generally applicable ideal vector is not likely to exist. We and others have recently turned to gene therapy using diverse suicide genes, cytokines, proapoptotic or antiangiogenic moieties via liposome-mediated gene transfer, 32,[41][42][43] or by using retroviral, adenoassociated or adenoviral vectors that were consequently used to transduce cancer cells in vitro and in vivo, 32,[44][45][46][47][48] Although these studies offer new alternatives and are potentially promising, they nevertheless face many of the obstacles that are inherent to their respective systems.…”

Section: Discussionmentioning

confidence: 99%

Replication-deficient rSV40 mediate pancreatic gene transfer and long-term inhibition of tumor growth

et al. 2006

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Pancreatic cancer is one of the most aggressive and devastating human malignancies. There is an urgent need for more effective therapy for patients with advanced disease. In this context, genetic therapy potentially represents a rational new approach to treating pancreatic cancer, which could provide an adjunct to conventional options. Because of the promise of recombinant SV40 vectors, we tested their ability to deliver a transgene, and to target a transcript, so as to inhibit pancreatic tumors growth in vivo. BxPC3 and Capan-1 cells were efficiently transduced using SV40 vectors without selection, as compared to synthetic vectors PEI. SV40 vectors were as efficient as adenoviral vectors, and provided long-term transgene expression. Next, we devised a SV40-derived, targeted gene therapy approach of pancreatic cancer, by combining hTR tumor-specific promoter with sst2 somatostatin receptor tumor-suppressor gene. In vitro cell proliferation was strongly impaired following administration of SV(hTR-sst2). SV40-derived sst2-mediated antiproliferative effect was dependent on the local production of somatostatin. In vivo, intratumoral gene transfer of sst2 using rSV40 vectors resulted in a marked inhibition of Capan-1 tumor progression, and proliferation. These results represent the initial steps toward a novel approach to the gene therapy of pancreatic cancer using SV40 as a vector.

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Enhanced gene transfer and cell death following p53 gene transfer using photochemical internalisation of glucosylated PEI‐DNA complexes

Abstract: PCI increases glucosylated-PEI-mediated p53 gene transfer, apoptosis as well as cell death in mutant p53 human cancer cells.

Cited by 49 publications

References 45 publications

P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab

P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab

Photochemical internalisation of chemotherapy potentiates killing of multidrug-resistant breast and bladder cancer cells

Replication-deficient rSV40 mediate pancreatic gene transfer and long-term inhibition of tumor growth

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