Radiosensitizing effect of epothilone B on human epithelial cancer cells

Baumgart, Tonja; Klautke, Günther; Kriesen, Stephan; Kuznetsov, Sergei A.; Weiss, Dieter G.; Fietkau, R.; Hildebrandt, Guido; Manda, Katrin

doi:10.1007/s00066-011-0029-4

Cited by 12 publications

(8 citation statements)

References 41 publications

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“…The interaction modality between photons or protons and Epothilone B in A549 and U251MG cells is slightly synergistic. Our results with photon beam on A549 cells are in agreement with those of Baumgart (Baumgart et al 2012), who found for the same cell line a synergistic effect of Epothilone B used in combination with photon beams irradiation. As far as we know there are no published studies on the use of Epothilone B in combination with proton beam irradiation on A549 or U251MG cells.…”

Section: Discussionsupporting

confidence: 93%

“…To measure cell clonogenic survival, cells were detached from the flask immediately after irradiation using 0.25% Trypsin-EDTA, counted, reseeded in 5 T25 flasks for each dose/ treatment at suitable concentration and incubated for about 13 days. Incubation time intervals for clonogenic survival of these human cell lines reported in the literature are between 10 and 14 days (Baumgart et al 2012, Rohrer Bley et al 2009. The cells were then fixed with ethanol and stained with 10% Giemsa solution and colonies consisting of more than 50 cells were scored as survivors.…”

Section: Clonogenic Assaymentioning

confidence: 99%

“…Epothilone B has shown antivascular and antiangiogenic effects (Ferretti et al 2005, Bocci et al 2002 and the ability to effectively inhibit cells' migration at non-cytotoxic concentration (Pagano et al 2012, Furmanova-Hollenstein et al 2013. It was also demonstrated that Epothilone B reduces DNA repair capability of tumour cells (Baumgart et al 2012(Baumgart et al , 2015 .…”

Section: Introductionmentioning

confidence: 98%

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Combining proton or photon irradiation with epothilone B. An in vitro study of cytotoxicity in human cancer cells

Bettega¹,

Calzolari²,

Ciocca³

et al. 2017

Biomed. Phys. Eng. Express

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Recently, the use of proton beams in cancer therapy is spreading out and tumour treatment modalities combining radiosensitizing chemical agents with irradiation are under investigation in order to achieve greater tumour local control and reduce the probability of distant failures. The combined treatment modality of radiation and the clinically relevant microtubule-stabilizing compound Epothilone B is a promising approach for anticancer therapy. In the present study, we investigated the cytotoxicity of a Spread Out Bragg Peak (SOBP) proton beam , as well as of 6 MV photons, in human glioblastoma (U251 MG) and lung adenocarcinoma (A549) cells pretreated for 24 h, or not, with Epothilone B at concentrations of 0.125 and 0.075 nM respectively. Proton irradiation was performed at the middle position of an actively modulated SOBP (12-18 cm depth in water) and cell survival was evaluated by colony forming assay. For both cell lines, survival curves after proton or photon irradiation alone showed a linear quadratic behaviour with a proton RBE (Relative Biological Effectiveness), compared with photons at 10% survival, of 1.5 ± 0.2. Treatment of the cells with Epothilone B at subnanomolar concentration has an anticlonogenic effect. Furthermore, differently from the results found with radiation alone, the survival curves for the combined treatment Epothilone B-radiation showed a linear trend and analysis of the interaction of the two cytotoxic agents indicated a slight synergism. These data provide a radiobiological basis for further experiments, as well as clinical studies.

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Section: Discussionsupporting

confidence: 93%

Section: Clonogenic Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Combining proton or photon irradiation with epothilone B. An in vitro study of cytotoxicity in human cancer cells

Bettega¹,

Calzolari²,

Ciocca³

et al. 2017

Biomed. Phys. Eng. Express

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“…Though some links between those two machineries have been reported (Baschal et al, 2006; Lee et al, 2010; Lee et al, 2011; Xie et al, 2011), the conserved link described here points to a more general connection, whose exact physiological role and mechanistic details - in particular the cytoskeletal DDR target(s) involved - will need to be clarified. This might be of particular therapeutic relevance as a combination of cytostatic doses of DNA-damaging drugs with microtubule drugs has been shown to result in selective cytotoxicity and radio-/chemo-sensitisation in some cancer cells (Baumgart et al, 2012; Blagosklonny et al, 2000; Lee et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

A Genomic Multiprocess Survey of Machineries that Control and Link Cell Shape, Microtubule Organization, and Cell-Cycle Progression

et al. 2014

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Understanding cells as integrated systems requires that we systematically decipher how single genes affect multiple biological processes and how processes are functionally linked. Here, we used multiprocess phenotypic profiling, combining high-resolution 3D confocal microscopy and multiparametric image analysis, to simultaneously survey the fission yeast genome with respect to three key cellular processes: cell shape, microtubule organization, and cell-cycle progression. We identify, validate, and functionally annotate 262 genes controlling specific aspects of those processes. Of these, 62% had not been linked to these processes before and 35% are implicated in multiple processes. Importantly, we identify a conserved role for DNA-damage responses in controlling microtubule stability. In addition, we investigate how the processes are functionally linked. We show unexpectedly that disruption of cell-cycle progression does not necessarily affect cell size control and that distinct aspects of cell shape regulate microtubules and vice versa, identifying important systems-level links across these processes.

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“…(56,57) Furthermore there seems to be a tendency toward a concentration-dependent increase in DNA double strand breaks after combined treatment, suggesting a reduction of DSB repair capacity as an additional mechanism of sensitization. (46) Reoxygenation theory (biological cooperation, temporal modulation). The enhanced radiation response of combined treatment with microtubule stabilizing agents and ionizing radiation has also been attributed to "tumor cell reoxygenation".…”

Section: Rationale For the Combined Use Of Irradiation And Cytotoxic mentioning

confidence: 99%

Microtubule stabilising agents and ionising radiation: Multiple exploitable mechanisms for combined treatment

Bley

Furmanova

Orlowski

et al. 2013

European Journal of Cancer

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Combined radiochemotherapy treatment modalities are in use for many indications and therefore of high interest. Even though a combined modality in clinical use is often driven by prag-matic aspects, mechanistic preclinical-based concepts of interaction are of importance in order to translate and implement an optimal combination and scheduling of two modalities into the clinics. The use of microtubule stabilizing agents is a promising strategy for anti-cancer therapy as a part of combined treatment modality with ionizing radiation. Traditionally, microtubule targeting agents are classified as cytotoxic chemotherapeutics and are mostly used in a maxi-mally tolerated dose regimen. Apart from direct cytotoxicity and similar to mechanisms of mo-lecular targeting agents, microtubule stabilizing agents interfere with multiple cellular process-es, which can be exploited as part of combined treatment modalities. Recent preclinical investi-gations on the combination of ionizing radiation and microtubule stabilizing agents reveal new mechanistic interactions on the cellular and tumor level and elucidate the supra-additive tumor response observed particularly in vivo. The major focus on the mechanism of interaction was primarily based on radiosensitization due to cell cycle arrest in the most radiosensitive G2/M-phase of the cell cycle. However, other mechanisms of interaction such as reoxygenation and direct as well as indirect endothelial damage have also been identified. In this review we sum-marize and allocate additive and synergistic effects induced by the combined treatment of clini-cally relevant microtubule stabilizing agents and ionizing radiation along a described radiobio-logical framework encompassing distinct mechanisms relevant for exploiting the combination of drugs and ionizing radiation. primarily based on radiosensitization due to cell cycle arrest in the most radiosensitive G2/Mphase of the cell cycle. However, other mechanisms of interaction such as reoxygenation and direct as well as indirect endothelial damage have also been identified. In this review we summarize and allocate additive and synergistic effects induced by the combined treatment of clinically relevant microtubule stabilizing agents and ionizing radiation along a described radiobiological framework encompassing distinct mechanisms relevant for exploiting the combination of drugs and ionizing radiation.

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Radiosensitizing effect of epothilone B on human epithelial cancer cells

Cited by 12 publications

References 41 publications

Combining proton or photon irradiation with epothilone B. An in vitro study of cytotoxicity in human cancer cells

Combining proton or photon irradiation with epothilone B. An in vitro study of cytotoxicity in human cancer cells

A Genomic Multiprocess Survey of Machineries that Control and Link Cell Shape, Microtubule Organization, and Cell-Cycle Progression

Microtubule stabilising agents and ionising radiation: Multiple exploitable mechanisms for combined treatment

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