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Figure S6 from β-Cryptoxanthin Synergistically Enhances the Antitumoral Activity of Oxaliplatin through ΔNP73 Negative Regulation in Colon Cancer

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posted on 2023-03-31, 18:46 authored by Coral San Millán, Beatriz Soldevilla, Paloma Martín, Beatriz Gil-Calderón, Marta Compte, Belén Pérez-Sacristán, Encarnación Donoso, Cristina Peña, Jesús Romero, Fernando Granado-Lorencio, Félix Bonilla, Gemma Domínguez

Figure S6. Quantification of Î”Np73 mRNA levels in normal colon mucosa from mice after the treatment with vehicle, Î²-cryptoxanthin 10 Î¼M, oxaliplatin 3 mg/Kg and the combined regimen of Î²-cryptoxanthin 10 Î¼M and oxaliplatin 3 mg/Kg. Mean {plus minus} standard deviation of at least four samples per group is represented.

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ARTICLE ABSTRACT

Background: The acquired resistance to chemotherapy represents the major limitation in the treatment of cancer. New strategies to solve this failure and improve patients' outcomes are necessary. The cancer preventive effect of β-cryptoxanthin has been widely described in population studies. Few reports support its putative use as an antitumoral compound. Here we focus on the therapeutic potential of β-cryptoxanthin individually or in combination with oxaliplatin in colon cancer and try to decipher the molecular basis underlying its effect.Methods: Apoptosis, viability and proliferation assays, mouse models, and an intervention study in 20 healthy subjects were performed. A PCR array was carried out to unravel the molecular putative basis of the β-cryptoxanthin effect, and further signaling experiments were conducted. Comet Assay was completed to evaluate the genotoxicity of the treatments.Results: β-Cryptoxanthin differentially regulates the expression of the P73 variants in vitro, in vivo, and in a human intervention study. This carotenoid decreases the proliferation of cancer cells and cooperates with oxaliplatin to induce apoptosis through the negative regulation of ΔNP73. The antitumoral concentrations of oxaliplatin decrease in the presence of β-cryptoxanthin to achieve same percentage of growth inhibition. The genotoxicity in peripheral blood mononuclear cells of mice decreased in the combined treatment.Conclusions: We propose a putative novel therapeutic strategy for the treatment of colon cancer based on the combination of β-cryptoxanthin and oxaliplatin. The combined regimen produced more benefit than either individual modality without increasing side effects. In addition, the concentration-limiting toxicity of oxaliplatin is reduced in the presence of the carotenoid. Clin Cancer Res; 21(19); 4398–409. ©2015 AACR.