Laboratório de Biologia Celular de Gliomas, Programa de Pós-Graduação em Biologia Celular e do Desenvolvimento, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Laboratório de Neuroquímica-4, Programa de Pós-Graduação em Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Anticancer Res. 2020 Dec;40(12):6799-6815. doi: 10.21873/anticanres.14703.
BACKGROUND/AIM: Glioblastomas (GBMs) are the most malignant primary brain tumor. New treatment strategies against the disease are urgently needed, as therapies are not completely efficient. In this study, we evaluated the antitumorigenic activity of the carotenoid fucoxanthin (Fx) on human GBM cells in vitro.
GBM1 cell viability and proliferation was assessed by MTT reduction, Ki67 and single cell cloning assays. GBM1 migration and invasion were analyzed by wound healing and Transwell assays. Apoptosis and necrosis were analyzed by flow cytometry, and the mitochondrial membrane potential (ΔΨm) by the selective fluorescent dye tetramethylrhodamine ethyl ester. Cell morphology was analyzed through scanning electron microscopy and transmission electron microscopy. Fx anti-angiogenic effect was assessed by the CAM ex ovo assay.
Fx decreased cell viability in a concentration-dependent manner (40-100 μ M) in GBM1, A172 and C6 cell lines and was not cytotoxic to murine astrocytes. In addition, Fx inhibited the proliferation and clonogenic potential, and decreased migration and invasion of GBM1 cells. Furthermore, Fx induced apoptosis, loss of ΔΨm and ultrastructural alterations in GBM1. Fx-treated GBM1 cells-conditioned medium reduced the quail yolk membrane vascularity.
Fx induces cytotoxicity, anti-proliferative, anti-invasive and anti-angiogenic effects on GBM1 cells.
背景/目的:胶质母细胞瘤(GBM)是最恶性的原发性脑肿瘤。由于治疗并不完全有效,因此迫切需要针对这种疾病的新治疗策略。在这项研究中,我们评估了类胡萝卜素岩藻黄质(Fx)对体外人 GBM 细胞的抗肿瘤活性。
通过 MTT 还原、Ki67 和单细胞克隆测定评估 GBM1 细胞活力和增殖。通过划痕愈合和 Transwell 测定分析 GBM1 迁移和侵袭。通过流式细胞术分析细胞凋亡和坏死,通过选择性荧光染料四甲基罗丹明乙酯分析线粒体膜电位(ΔΨm)。通过扫描电子显微镜和透射电子显微镜分析细胞形态。通过鸡胚绒毛尿囊膜外植体测定评估 Fx 的抗血管生成作用。
Fx 在 GBM1、A172 和 C6 细胞系中以浓度依赖性方式(40-100 μM)降低细胞活力,对鼠星形胶质细胞无细胞毒性。此外,Fx 抑制了 GBM1 细胞的增殖和克隆形成潜力,并降低了其迁移和侵袭能力。此外,Fx 诱导 GBM1 细胞凋亡、丧失 ΔΨm 和超微结构改变。Fx 处理的 GBM1 细胞条件培养基减少了鹌鹑卵黄膜的血管生成。
Fx 对 GBM1 细胞具有细胞毒性、抗增殖、抗侵袭和抗血管生成作用。