Faculty of Pharmacy, Department of Biochemistry, Ankara University, Ankara, Turkey.
Phytother Res. 2019 Feb;33(2):397-402. doi: 10.1002/ptr.6233. Epub 2018 Nov 19.
In cancer treatment, which is a major cause of mortality today, combination studies with clinically used chemotherapeutics are becoming increasingly important as much as investigating the effects of novel natural compounds. In this context, phytoalexins constitute an important group due to their unique structure. Brassinin is an essential indole phytoalexin and is a biosynthetic precursor for other phytoalexins. The purpose of this study was to evaluate the anticancer effects of brassinin in combination with imatinib in SW480 cells. In the study, it was observed that brassinin-imatinib combination significantly increased cytotoxicity compared with the single treatment of both compounds and inhibited cell cycle at G0/G1 phase. Annexin V binding and fluorescence imaging assays showed that the combination of brasinin-imatinib induces apoptosis in a dose-dependent manner. Furthermore, the effect of brassinin on the activity of MMP-9 in SW480 cells was evaluated for the first time, and it was detected that MMP-9 activity was significantly reduced. The combination of brassinin-imatinib was found to inhibit MMP-9 activity as well as relative MMP-9 gene expression on a higher level compared with control and compounds alone. Our findings have revealed that the combination of brassinin-imatinib synergistically induces cytotoxicity and apoptosis in SW480 cells. The findings on MMP-9 downregulation have also revealed the anti-metastatic potential of treatment.
在癌症治疗中,组合研究与临床使用的化疗药物变得越来越重要,因为它不仅可以调查新型天然化合物的作用,还可以调查癌症的作用。在这方面,植物抗毒素由于其独特的结构构成了一个重要的研究领域。油菜素内酯是一种重要的吲哚植物抗毒素,也是其他植物抗毒素的生物合成前体。本研究旨在评估油菜素内酯与伊马替尼联合应用于 SW480 细胞的抗癌作用。在研究中,与单独使用两种化合物相比,油菜素内酯-伊马替尼联合显著增加了细胞毒性,并抑制细胞周期进入 G0/G1 期。 Annexin V 结合和荧光成像检测表明,油菜素内酯-伊马替尼联合以剂量依赖的方式诱导细胞凋亡。此外,首次评估了油菜素内酯对 SW480 细胞中 MMP-9 活性的影响,检测到 MMP-9 活性显著降低。与对照组和单独使用化合物相比,油菜素内酯-伊马替尼联合能更有效地抑制 MMP-9 活性和相对 MMP-9 基因表达。我们的研究结果表明,油菜素内酯-伊马替尼联合在 SW480 细胞中协同诱导细胞毒性和细胞凋亡。MMP-9 下调的发现也揭示了治疗的抗转移潜力。