Belakavadi Madesh, Salimath Bharathi P
Department of Applied Botany and Biotechnology, University of Mysore, Karnataka, India.
Mol Cell Biochem. 2005 May;273(1-2):57-67. doi: 10.1007/s11010-005-7717-2.
One of the most clinically relevant biological activities of curcumin is its anti-cancer property, implicating multiple intracellular pathways in the process. In the present report, we investigated the effect of curcumin on the activation of apoptotic and anti-angiogenic pathways in Ehrlich Ascites Tumor (EAT) cells. Treatment with curcumin in vivo resulted in inhibition of proliferation of EAT cells and ascites formation. Further, we demonstrate that the induction of apoptosis in EAT cells showed nuclear condensation, DNA fragmentation and translocation of caspase-activated DNase (CAD) to nucleus upon curcumin treatment. Curcumin-induced apoptosis is mediated through activation of caspase-3, which is specifically inhibited by the caspase-3 inhibitor, Ac-DEVD-CHO. On the other hand, the decreased secretion of ascites by EAT cells is corroborated by reduction in VEGF secretion upon curcumin treatment. Further, CD31 immunohistological staining of peritoneum sections in curcumin-treated mice suggests its efficacy in acting as anti-angiogenic compound in EAT cells by inhibiting proliferation of endothelial cells in mouse peritoneum. However, immunoflurescence studies of NF-kB revealed that the inhibition of nuclear translocation of NF-kB p65, a transcription factor required for VEGF gene expression, in curcumin-treated EAT cells. These results suggest a further possible clinical application of this diet-derived compound curcumin, as both proapoptotic and anti-angiogenic compound in association with conventional chemotherapeutic agents.
姜黄素最具临床相关性的生物学活性之一是其抗癌特性，在此过程中涉及多种细胞内途径。在本报告中，我们研究了姜黄素对艾氏腹水瘤（EAT）细胞凋亡和抗血管生成途径激活的影响。体内用姜黄素处理导致EAT细胞增殖抑制和腹水形成受抑。此外，我们证明姜黄素处理后EAT细胞凋亡诱导表现为核浓缩、DNA片段化以及半胱天冬酶激活的脱氧核糖核酸酶（CAD）转位至细胞核。姜黄素诱导的凋亡通过半胱天冬酶-3的激活介导，半胱天冬酶-3抑制剂Ac-DEVD-CHO可特异性抑制该过程。另一方面，姜黄素处理后EAT细胞腹水分泌减少，这与VEGF分泌减少相一致。此外，姜黄素处理小鼠腹膜切片的CD31免疫组织化学染色表明，它通过抑制小鼠腹膜内皮细胞增殖，在EAT细胞中作为抗血管生成化合物发挥作用。然而，NF-κB的免疫荧光研究显示，在姜黄素处理的EAT细胞中，VEGF基因表达所需的转录因子NF-κB p65的核转位受到抑制。这些结果表明，这种源自饮食的化合物姜黄素作为促凋亡和抗血管生成化合物，与传统化疗药物联合使用可能具有进一步的临床应用价值。
