García-Vilas Javier A, Quesada Ana R, Medina Miguel A
Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, and IBIMA (Biomedical Research Institute of Málaga).
1] Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, and IBIMA (Biomedical Research Institute of Málaga) [2] CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga, Spain.
Sci Rep. 2015 Jan 26;5:8021. doi: 10.1038/srep08021.
Damnacanthal, an anthraquinone present in noni plants, targets several tyrosine kinases and has antitumoral effects. This study aims at getting additional insight on the potential of damnacanthal as a natural antitumor compound. The direct effect of damnacanthal on c-Met was tested by in vitro activity assays. Additionally, Western blots of c-Met phosphorylation in human hepatocellular carcinoma Hep G2 cells were performed. The antitumor effects of damnacanthal were tested by using cell growth, soft agar clonogenic, migration and invasion assays. Their mechanisms were studied by Western blot, and cell cycle, apoptosis and zymographic assays. Results show that damnacanthal targets c-Met both in vitro and in cell culture. On the other hand, damnacanthal also decreases the phosphorylation levels of Akt and targets matrix metalloproteinase-2 secretion in Hep G2 cells. These molecular effects are accompanied by inhibition of the growth and clonogenic potential of Hep G2 hepatocellular carcinoma cells, as well as induction of Hep G2 apoptosis. Since c-Met has been identified as a new potential therapeutical target for personalized treatment of hepatocellular carcinoma, damnacanthal and noni extract supplements containing it could be potentially interesting for the treatment and/or chemoprevention of hepatocellular carcinoma through its inhibitory effects on the HGF/c-Met axis.
印度枸杞所含的蒽醌类化合物—— damnacanthal，作用于多种酪氨酸激酶，具有抗肿瘤作用。本研究旨在进一步深入了解 damnacanthal 作为一种天然抗肿瘤化合物的潜力。通过体外活性测定试验了 damnacanthal 对 c-Met 的直接作用。此外，还对人肝癌 Hep G2 细胞中的 c-Met 磷酸化进行了蛋白质免疫印迹分析。通过细胞生长、软琼脂克隆形成、迁移和侵袭试验检测了 damnacanthal 的抗肿瘤作用。通过蛋白质免疫印迹、细胞周期、凋亡和酶谱分析研究了其作用机制。结果表明，damnacanthal 在体外和细胞培养中均作用于 c-Met。另一方面，damnacanthal 还降低了 Hep G2 细胞中 Akt 的磷酸化水平，并作用于基质金属蛋白酶-2 的分泌。这些分子效应伴随着对 Hep G2 肝癌细胞生长和克隆形成潜力的抑制，以及对 Hep G2 细胞凋亡的诱导。由于 c-Met 已被确定为肝细胞癌个性化治疗的一个新的潜在治疗靶点，damnacanthal 以及含有它的诺丽提取物补充剂可能因其对 HGF/c-Met 轴的抑制作用而对肝细胞癌的治疗和/或化学预防具有潜在的意义。
