Synergistic Effect of the Combination of Polyphenols with Gemcitabineon Pancreatic Cancer Cell line AsPC-1

Abstract

Sarah Hassan Jean Peluso, Guy Fuhrmann and Genevieve Ubeaud-Sequie

In our diet, polyphenols are micronutrients with an important role in the prevention of degenerative diseases such as cancer and cardiovascular diseases. Particularly, Pancreatic cancer is one of the most aggressive cancers, with only about 5% of patients surviving 5 years past the initial diagnosis. Despite advances with current chemotherapy combinations, overall survival outcomes are still require novel therapeutic approaches. Here, we examined the efficacy of combined treatments of polyphenols and gemcitabine the standard of treatment for patients with metastatic pancreatic cancer in human pancreatic cancer cells. For that purpose, the pro-apoptic effects of gemcitabine were studied on the human pancreatic cell line AsPC1 in presence or absence of several polyphenols, in order to evaluate if they latter are able to potentialize gemcitabine cytotoxicity. Our study aims to investigate the implication of MDR1 (multidrug transporter)in resistance to gemcitabine and if the studied polyphenol could target this drug efflux pump in AsPC-1 cells by flow cytometric analysis. We observed that 5µg/ml gemcitabine in combination with 15 µg/ml of selected polyphenol (Catechin, Quercetin, Bergamottin, Rhamnetin) was more effective than gemcitabine alone, by increased in the percentage of dead cells up to 60%. Morever our results demonstrated that some polyphenols (Quercetin) inhibit the efflux activity of MDR1. Our study in vitro suggests therefore that chemotherapy with gemcitabine might be significantly increased upon combination with specific polyphenol. In conclusion, polyphenols may be promising agents for novel combination therapy since they potentialize the cytotoxic activity of gemcitabine to eradicate pancreatic cancer and therefore the cellular resistance.

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