Benvenuto Monica, Mattera Rosanna, Masuelli Laura, Taffera Gloria, Andracchio Orlando, Tresoldi Ilaria, Lido Paolo, Giganti Maria Gabriella, Godos Justyna, Modesti Andrea, Bei Roberto
a Department of Clinical Sciences and Translational Medicine, Faculty of Medicine , University of Rome "Tor Vergata" , Rome , Italy.
b Department of Experimental Medicine , "Sapienza Università di Roma" , Rome , Italy.
Int J Food Sci Nutr. 2017 May;68(3):298-312. doi: 10.1080/09637486.2016.1236077. Epub 2016 Sep 27.
Racemic Gossypol [(±)-GOS], composed of both (-)-GOS and (+)-GOS, is a small BH3-mimetic polyphenol derived from cotton seeds. (±)-GOS has been employed and well tolerated by cancer patients. Head and neck carcinoma (HNC) represents one of the most fatal cancers worldwide, and a significant proportion of HNC expresses high levels of antiapoptotic Bcl-2 proteins. In this study, we demonstrate that (±)-GOS inhibits cell proliferation and induces apoptosis and autophagy of human pharynx, tongue, and salivary gland cancer cell lines and of mouse salivary gland cancer cells (SALTO). (±)-GOS was able to: (a) decrease the ErbB2 protein expression; (b) inhibit the phosphorylation of ERK1/2 and AKT; (c) stimulate p38 and JNK1/2 protein phosphorylation. (±)-GOS administration was safe in BALB/c mice and it reduced the growth of transplanted SALTO cells in vivo and prolonged mice median survival. Our results suggest the potential role of (±)-GOS as an antitumor agent in HNC patients.
消旋棉酚[（±）-GOS]由（-）-GOS和（+）-GOS组成，是一种源自棉籽的小分子BH3模拟多酚。（±）-GOS已被癌症患者使用且耐受性良好。头颈癌（HNC）是全球最致命的癌症之一，相当一部分HNC表达高水平的抗凋亡Bcl-2蛋白。在本研究中，我们证明（±）-GOS抑制人咽、舌和唾液腺癌细胞系以及小鼠唾液腺癌细胞（SALTO）的细胞增殖并诱导其凋亡和自噬。（±）-GOS能够：（a）降低ErbB2蛋白表达；（b）抑制ERK1/2和AKT的磷酸化；（c）刺激p38和JNK1/2蛋白磷酸化。（±）-GOS给药对BALB/c小鼠是安全的，它能在体内减少移植的SALTO细胞的生长并延长小鼠的中位生存期。我们的结果表明（±）-GOS作为一种抗肿瘤药物在HNC患者中具有潜在作用。
