Harada Koji, Ferdous Tarannum, Itashiki Yasutaka, Takii Michiyo, Mano Takamichi, Mori Yoshihide, Ueyama Yoshiya
Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
Int J Oncol. 2009 Nov;35(5):1025-35. doi: 10.3892/ijo_00000417.
Cepharanthine is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata, which is widely used for the treatment of many acute and chronic diseases, and can exert antitumor effects on several human cancer cell lines. However, little is known about the detailed mechanisms of the antitumor activity of Cepharanthine. In the present study, we determined whether Cepharanthine could suppress angiogenesis and growth of human oral squamous cell carcinoma (OSCC) cells in vitro and in vivo. Cepharanthine significantly inhibited expression of two major pro-angiogenic molecules, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in cultured cells and in cells implanted into the subcutaneous tissue of nude mice. Also, Cepharanthine inhibited the nuclear factor-kappaB (NF-kappaB) activity in human OSCC cells in vitro and in vivo. The decreased expression of VEGF and IL-8 correlated with decreased tumor cell growth and decreased vascularization in vitro and in vivo. These findings suggest that Cepharanthine can suppress angiogenesis and growth of OSCC cells by inhibiting expression of VEGF and IL-8 involved in the blockade of NF-kappaB activity.
千金藤素是从千金藤中提取的一种双苄基异喹啉生物碱，广泛用于治疗多种急慢性疾病，并能对多种人类癌细胞系发挥抗肿瘤作用。然而，关于千金藤素抗肿瘤活性的详细机制知之甚少。在本研究中，我们确定了千金藤素是否能在体外和体内抑制人口腔鳞状细胞癌（OSCC）细胞的血管生成和生长。千金藤素显著抑制培养细胞和植入裸鼠皮下组织的细胞中两种主要促血管生成分子血管内皮生长因子（VEGF）和白细胞介素-8（IL-8）的表达。此外，千金藤素在体外和体内均可抑制人OSCC细胞中的核因子-κB（NF-κB）活性。VEGF和IL-8表达的降低与体外和体内肿瘤细胞生长的减少及血管化程度的降低相关。这些发现表明，千金藤素可通过抑制参与NF-κB活性阻断的VEGF和IL-8的表达来抑制OSCC细胞的血管生成和生长。
