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木犀草素可诱导神经母细胞瘤脑肿瘤细胞凋亡、G0/G1期细胞周期生长停滞以及线粒体膜电位丧失。

Luteolin induces apoptosis, G0/G1 cell cycle growth arrest and mitochondrial membrane potential loss in neuroblastoma brain tumor cells.

作者信息

Wang F, Gao F, Pan S, Zhao S, Xue Y

机构信息

Department of Neurosurgery, Affiliated Hospital of Weifang Medical University, Shandong Province, China.

Department of Neurosurgery, People's Hospital of Anqiu City, Shandong Province, China.

出版信息

Drug Res (Stuttg). 2015 Feb;65(2):91-5. doi: 10.1055/s-0034-1372648. Epub 2014 May 15.

Abstract

The objective of the present research work was to evaluate the anticancer properties of luteolin against SH-SY5Y neuroblastoma tumor cell line. Cell viability was evaluated by MTT assay after luteolin treatment. Lactate dehydrogenase assay (LDH) was used to evaluate the extent of cell death induced by luteolin. Flow-cytometry was used to examine the effect of luteolin on cell cycle progression and mitochondrial membrane potential (ΛΨm) in SH-SY5Y cells. Phase-contrast microscopy detected the morphological changes in SH-SY5Y cells after luteolin treatment. Our results demonstrated that luteolin induced dose-dependent as well as time-dependent growth inhibition of SH-SY5Y cells with IC50 value of 27.1 µM after 12 h of incubation. Further, luteolin induced significant release of LDH from SH-SY5Y cell cultures following luteolin treatment significantly at 25 and 50 µM doses which corresponds to significant cell death. Phase-contrast microscopy revealed characteristic morphological features of apoptosis induced by luteolin. Flow-cytometry revealed that luteolin induced G0/G1 cell cycle growth arrest in SH-SY5Y cells. Luteolin also induced a progressive and dose-dependent reduction in the mitochondrial membrane potential. In conclusion, our results revealed that luteolin significantly induces growth inhibition of SH-SY5Y tumor cells by inducing apoptosis accompanied with G0/G1 cell cycle growth arrest and concomitant loss in mitochondrial membrane potential (ΛΨm). As such luteolin can be developed as a potent anticancer agent against brain tumor disorders.

摘要

本研究工作的目的是评估木犀草素对SH-SY5Y神经母细胞瘤肿瘤细胞系的抗癌特性。木犀草素处理后,通过MTT法评估细胞活力。乳酸脱氢酶测定法(LDH)用于评估木犀草素诱导的细胞死亡程度。流式细胞术用于检测木犀草素对SH-SY5Y细胞细胞周期进程和线粒体膜电位(ΔΨm)的影响。相差显微镜检测木犀草素处理后SH-SY5Y细胞的形态变化。我们的结果表明,木犀草素诱导SH-SY5Y细胞出现剂量依赖性和时间依赖性生长抑制,孵育12小时后IC50值为27.1μM。此外,木犀草素处理后,在25和50μM剂量下,SH-SY5Y细胞培养物中LDH显著释放,这对应于显著的细胞死亡。相差显微镜显示了木犀草素诱导的凋亡特征性形态学特征。流式细胞术显示,木犀草素诱导SH-SY5Y细胞G0/G1期细胞周期生长停滞。木犀草素还诱导线粒体膜电位逐渐降低且呈剂量依赖性。总之,我们的结果表明,木犀草素通过诱导凋亡,同时伴有G0/G1期细胞周期生长停滞和线粒体膜电位(ΔΨm)的相应丧失,显著诱导SH-SY5Y肿瘤细胞生长抑制。因此,木犀草素可开发成为一种有效的抗脑肿瘤疾病抗癌药物。

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