Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
J Pharmacol Sci. 2013;121(3):192-9. doi: 10.1254/jphs.12137fp.
Aggressive tumor growth and diffuse tissue invasion are hallmarks of malignant glioma. Embelin is an active compound identified as a novel XIAP inhibitor from the Embelia ribes that exhibits various medicinal effects including anti-inflammatory and anti-cancer activities. In the present study, we investigated whether embelin could have a therapeutic effect in glioma. We found that embelin suppressed proliferation of human glioma cells, but not in normal immortalized human astrocytes. In addition, embelin induced apoptosis in human glioma cells by inhibiting NF-κB, which is a crucial transcription factor associated with several human diseases including cancer and controls multiple genes involved in tumor progression such as cell proliferation and survival. Intriguingly, embelin had no inhibitory effect on XIAP in glioma cells even though discovered as an XIAP inhibitor, but instead inhibited NF-κB activity by reducing nuclear translocation of p65 through decreasing phosphorylation and proteasomal degradation of IκBα in glioma cells. Furthermore, p65 overexpression decreased embelin-induced apoptosis in glioma cells. Taken together these results indicate that embelin could be a potent novel therapeutic modality for glioma via blocking cancer cell proliferation and inducing apoptosis by inhibiting NF-κB activity.
侵袭性肿瘤生长和广泛的组织浸润是恶性脑胶质瘤的特征。棓丙酯是从石榴中鉴定出的一种新型 XIAP 抑制剂的活性化合物，具有多种药用作用，包括抗炎和抗癌作用。在本研究中，我们研究了棓丙酯是否对脑胶质瘤具有治疗作用。我们发现棓丙酯抑制了人胶质瘤细胞的增殖，但对正常永生化人星形胶质细胞没有作用。此外，棓丙酯通过抑制 NF-κB 诱导人胶质瘤细胞凋亡，NF-κB 是与包括癌症在内的几种人类疾病相关的关键转录因子，并且控制着与肿瘤进展相关的多个基因，如细胞增殖和存活。有趣的是，尽管棓丙酯被发现是 XIAP 抑制剂，但它对胶质瘤细胞中的 XIAP 没有抑制作用，而是通过减少磷酸化和蛋白酶体降解 IκBα 来减少 p65 的核易位，从而抑制 NF-κB 活性。此外，p65 的过表达减少了棓丙酯诱导的胶质瘤细胞凋亡。这些结果表明，棓丙酯通过抑制 NF-κB 活性来阻断癌细胞增殖并诱导细胞凋亡，可能成为治疗脑胶质瘤的一种有效新型治疗方法。
