Resveratrol potentiates the in vitro and in vivo anti-tumoral effects of curcumin in head and neck carcinomas
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Laura Masuelli1, Enrica Di Stefano1, Massimo Fantini2, Rosanna Mattera1, Monica Benvenuto2, Laura Marzocchella2, Pamela Sacchetti1, Chiara Focaccetti3, Roberta Bernardini3, Ilaria Tresoldi 2, Valerio Izzi2, Maurizio Mattei3, Giovanni Vanni Frajese4, Florigio Lista5, Andrea Modesti2 and Roberto Bei2
1 Department of Experimental Medicine, University of Rome “Sapienza”, Rome, Italy
2 Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Rome, Italy
3 STA, University of Rome “Tor Vergata”, Rome, Italy
4 Dipartimento di Scienze Motorie, Umane e della Salute, Università di Roma, Foro Italico
5 Centro Studi e Ricerche Sanità e Veterinaria Esercito, Rome, Italy
Roberto Bei, email:
Keywords: polyphenols, head and neck cancer, curcumin, resveratrol
Received: July 25, 2014 Accepted: September 25, 2014 Published: September 26, 2014
The survival rate of head and neck squamous cell carcinomas (HNSCC) patients has not considerably changed over the last two decades. Polyphenols inhibit the growth of cancer cells. We determined whether the combination of Resveratrol (RES) and Curcumin (CUR) enhanced their in vitro and in vivo antitumor activities on HNSCC cell lines compared to the single compounds. We provide evidence that RES potentiated the apoptotic effect and reduced the IC50 of CUR on HNSCC cell lines. The model of compounds interaction indicated the onset of an additive effect of the two compounds compared to the single treatment after decrease of their concentrations. RES+CUR compared to CUR increased the PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of LC3 II simultaneously with the formation of autophagic vacuoles. RES and CUR induced cytoplasmic NF-κB accumulation. RES+CUR administrations were safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) more efficiently than CUR. Overall, combinations of CUR and RES was more effective in inhibiting in vivo and in vitro cancer growth than the treatment with CUR. Additional studies will be needed to define the therapeutic potential of these compounds in combination.
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