Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
Molecules. 2019 Aug 28;24(17):3127. doi: 10.3390/molecules24173127.
Fangchinoline (FCN) derived from Stephaniae tetrandrine S. Moore can be employed to treat fever, inflammation, rheumatism arthralgia, edema, dysuria, athlete's foot, and swollen wet sores. FCN can exhibit a plethora of anti-neoplastic effects although its precise mode of action still remains to be deciphered. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) can closely regulate carcinogenesis and thus we analyzed the possible action of FCN may have on these two signaling cascades in tumor cells. The effect of FCN on NF-κB and AP-1 signaling cascades and its downstream functions was deciphered using diverse assays in both human chronic myeloid leukemia (KBM5) and multiple myeloma (U266). FCN attenuated growth of both leukemic and multiple myeloma cells and repressed NF-κB, and AP-1 activation through diverse mechanisms, including attenuation of phosphorylation of IκB kinase (IKK) and p65. Furthermore, FCN could also cause significant enhancement in TNFα-driven apoptosis as studied by various molecular techniques. Thus, FCN may exhibit potent anti-neoplastic effects by affecting diverse oncogenic pathways and may be employed as pro-apoptotic agent against various malignancies.
来源于防己科千金藤属头花千金藤的粉防己碱（FCN）可用于治疗发热、炎症、风湿性关节炎、水肿、尿频、脚气病和湿疮。尽管其确切作用机制仍有待阐明，但 FCN 可以表现出多种抗肿瘤作用。核因子-κB（NF-κB）和激活蛋白-1（AP-1）可以密切调节致癌作用，因此我们分析了 FCN 对肿瘤细胞中这两个信号级联的可能作用。在人慢性髓性白血病（KBM5）和多发性骨髓瘤（U266）中使用多种测定法阐明了 FCN 对 NF-κB 和 AP-1 信号级联及其下游功能的影响。FCN 通过多种机制减弱了白血病和多发性骨髓瘤细胞的生长，并抑制了 NF-κB 和 AP-1 的激活，包括抑制 IκB 激酶（IKK）和 p65 的磷酸化。此外，FCN 还可以通过各种分子技术研究 TNFα 驱动的凋亡，从而导致显著增强。因此，FCN 通过影响多种致癌途径可能表现出有效的抗肿瘤作用，并可作为针对各种恶性肿瘤的促凋亡剂。
