Masuelli Laura, Di Stefano Enrica, Fantini Massimo, Mattera Rosanna, Benvenuto Monica, Marzocchella Laura, Sacchetti Pamela, Focaccetti Chiara, Bernardini Roberta, Tresoldi Ilaria, Izzi Valerio, Mattei Maurizio, Frajese Giovanni Vanni, Lista Florigio, Modesti Andrea, Bei Roberto
Department of Experimental Medicine, University of Rome "Sapienza", Rome, Italy.
Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Rome, Italy.
Oncotarget. 2014 Nov 15;5(21):10745-62. doi: 10.18632/oncotarget.2534.
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.
在过去二十年中，头颈部鳞状细胞癌（HNSCC）患者的生存率没有显著变化。多酚类物质可抑制癌细胞生长。我们研究了白藜芦醇（RES）和姜黄素（CUR）联合使用时，与单一化合物相比，是否能增强其对HNSCC细胞系的体外和体内抗肿瘤活性。我们提供的证据表明，RES增强了CUR对HNSCC细胞系的凋亡作用并降低了其半数抑制浓度（IC50）。化合物相互作用模型表明，在浓度降低后，与单一处理相比，两种化合物出现了加和效应。与CUR相比，RES+CUR增加了聚（ADP-核糖）聚合酶-1（PARP-1）的裂解、Bax/Bcl-2比值、细胞外信号调节激酶1（ERK1）和细胞外信号调节激酶2（ERK2）磷酸化的抑制以及微管相关蛋白1轻链3-II（LC3 II）的表达，同时伴有自噬空泡的形成。RES和CUR诱导细胞质中核因子κB（NF-κB）的积累。RES+CUR给药对BALB/c小鼠是安全的，并且比CUR更有效地抑制移植的涎腺癌细胞（SALTO）的生长。总体而言，CUR和RES联合使用在体内和体外抑制癌症生长方面比单独使用CUR更有效。需要进一步研究来确定这些化合物联合使用的治疗潜力。
