Lee Yee Qian, Rajadurai Pathmanathan, Abas Faridah, Othman Iekhsan, Naidu Rakesh
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya, Malaysia.
Laboratory of Natural Products, Faculty of Science, University Putra Malaysia, Seri Kembangan, Malaysia.
Front Mol Biosci. 2021 Apr 30;8:645856. doi: 10.3389/fmolb.2021.645856. eCollection 2021.
Curcumin analogs with excellent biological properties have been synthesized to address and overcome the poor pharmacokinetic profiles of curcumin. This study aims to investigate the cytotoxicity, anti-proliferative, and apoptosis-inducing ability of curcumin analog, MS13 on human glioblastoma U-87 MG, and neuroblastoma SH-SY5Y cells, and to examine the global proteome changes in these cells following treatment. Our current findings showed that MS13 induced potent cytotoxicity and anti-proliferative effects on both cells. Increased caspase-3 activity and decreased bcl-2 concentration upon treatment indicate that MS13 induces apoptosis in these cells in a dose- and time-dependent manner. The label-free shotgun proteomic analysis has defined the protein profiles in both glioblastoma and neuroblastoma cells, whereby a total of nine common DEPs, inclusive of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), alpha-enolase (ENO1), heat shock protein HSP 90-alpha (HSP90AA1), Heat shock protein HSP 90-beta (HSP90AB1), Eukaryotic translation initiation factor 5A-1 (EFI5A), heterogenous nuclear ribonucleoprotein K (HNRNPK), tubulin beta chain (TUBB), histone H2AX (H2AFX), and Protein SET were identified. Pathway analysis further elucidated that MS13 may induce its anti-tumor effects in both cells via the common enriched pathways, "Glycolysis" and "Post-translational protein modification." Conclusively, MS13 demonstrates an anti-cancer effect that may indicate its potential use in the management of brain malignancies.
人们已合成具有优异生物学特性的姜黄素类似物,以解决并克服姜黄素不良的药代动力学特征。本研究旨在调查姜黄素类似物MS13对人胶质母细胞瘤U - 87 MG细胞和神经母细胞瘤SH - SY5Y细胞的细胞毒性、抗增殖及诱导凋亡能力,并检测处理后这些细胞中的整体蛋白质组变化。我们目前的研究结果表明,MS13对这两种细胞均诱导产生了强大的细胞毒性和抗增殖作用。处理后caspase - 3活性增加和bcl - 2浓度降低表明,MS13以剂量和时间依赖性方式诱导这些细胞凋亡。无标记鸟枪法蛋白质组分析确定了胶质母细胞瘤和神经母细胞瘤细胞中的蛋白质谱,共鉴定出9种常见的差异表达蛋白,包括甘油醛 - 3 - 磷酸脱氢酶(GAPDH)、α - 烯醇化酶(ENO1)、热休克蛋白HSP 90 - α(HSP90AA1)、热休克蛋白HSP 90 - β(HSP90AB1)、真核翻译起始因子5A - 1(EFI5A)、不均一核核糖核蛋白K(HNRNPK)、微管蛋白β链(TUBB)、组蛋白H2AX(H2AFX)和SET蛋白。通路分析进一步阐明,MS13可能通过共同富集的通路“糖酵解”和“蛋白质翻译后修饰”在这两种细胞中诱导其抗肿瘤作用。总之,MS13显示出抗癌作用,这可能表明其在脑恶性肿瘤治疗中的潜在用途。