Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, 58, Zhongshan Road II, Guangzhou 510080, China.
Life Sci. 2013 Jan 17;92(1):55-62. doi: 10.1016/j.lfs.2012.10.023. Epub 2012 Nov 8.
Wogonin is one of the major constituents derived from Scutellaria Baicalensis, which has been reported to inhibit cell growth and/or induce apoptosis in various cancer cell lines. We aim to investigate the anticancer effects and associated mechanisms of wogonin on human multiple myeloma cell line in vitro.
Effects of wogonin on the proliferation, cell cycle progression, and apoptosis of human myeloma cells were examined in vitro. The proteins associated with the biological effects of wogonin were analyzed by immunoblotting and immunocytochemical staining. In addition, the binding mode of wogonin within crystal structure of Akt1 protein was also evaluated by molecular docking analysis using the CDOCKER algorithm in Discovery Studio.
Myeloma cell growth was attenuated by wogonin (70.4-352.0 μM) in a concentration-dependent manner. Cell cycle progression analysis and TUNEL assay showed that apoptosis was enhanced in wogonin-treated cells. Increased apoptosis was accompanied by decreased level of total-PARP, the arisen of PARP cleavage, significantly increased level of Bax protein and decreased level of Bcl-2 protein. Akt activity was suppressed and phosphorylation of Ser 473 residue was decreased in the wogonin-treated cells. Molecular docking analysis revealed wogonin could be stably docked into the ligand binding domain of Akt1 protein, and presented unique features of binding to Akt1, which indicated detailed interaction between wogonin and Akt signaling pathway.
As wogonin was effective in vitro in promotion of apoptosis of myeloma cell by Akt-modulated, Bax and Bcl-2 related intrinsic apoptotic pathway, wogonin may be a potential therapeutic agent against multiple myeloma.
汉黄芩素是黄芩的主要成分之一，已被报道可抑制多种癌细胞系的细胞生长和/或诱导细胞凋亡。我们旨在研究汉黄芩素在体外对人多发性骨髓瘤细胞系的抗癌作用及相关机制。
在体外研究汉黄芩素对人骨髓瘤细胞增殖、细胞周期进程和凋亡的影响。通过免疫印迹和免疫细胞化学染色分析与汉黄芩素生物学效应相关的蛋白质。此外，还通过 Discovery Studio 中的 CDOCKER 算法进行分子对接分析评估了汉黄芩素在 Akt1 蛋白晶体结构内的结合模式。
汉黄芩素（70.4-352.0 μM）以浓度依赖的方式减弱骨髓瘤细胞生长。细胞周期进程分析和 TUNEL 检测表明，汉黄芩素处理的细胞中凋亡增强。凋亡增加伴随着总 PARP 水平降低，PARP 切割出现，Bax 蛋白水平显著升高，Bcl-2 蛋白水平降低。汉黄芩素处理的细胞中 Akt 活性受到抑制，Ser 473 残基磷酸化减少。分子对接分析表明，汉黄芩素可稳定地结合到 Akt1 蛋白的配体结合域，并呈现出与 Akt1 结合的独特特征，表明汉黄芩素与 Akt 信号通路之间存在详细的相互作用。
由于汉黄芩素在体外通过 Akt 调节、Bax 和 Bcl-2 相关内在凋亡途径有效促进骨髓瘤细胞凋亡，因此汉黄芩素可能是多发性骨髓瘤的潜在治疗药物。
