库库比他E葡萄糖化物通过调节AMPK/PGK1/PKM2通路来诱导黑色素瘤癌细胞的亡
Mohammed Abdalla Hussein1, Aya Sayed Sallam1, Shaza Ahmed Mohamed1
1Department of Biotechnology, Faculty of Applied Health Science, October 6 University, Giza, Egypt.
库库比他E葡萄糖化物 (CEG) 通过阻止细胞循环和降低关键代谢酶的调节,有效地诱导黑色素瘤细胞的亡. 这种天然化合物在向癌细胞代谢和增殖方面表现有前途.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 植物衍生化合物库库比他素E葡萄糖化物 (CEG) 通过抑制癌细胞入侵和迁移,显示出抗癌性质.
- CEG机制包括亡诱导,自,细胞循环停止和动因细胞骨破坏.
研究的目的:
- 为了研究CEG对A375黑色素瘤细胞系的亡机制.
- 阐明CEG对细胞活力,细胞亡,亡以及黑色素瘤细胞中关键分子通路的影响.
主要方法:
- 针对A375细胞和特定酶 (PGK1,PKM2) 的CEG,确定了IC50值.
- 评估了细胞活力,细胞亡,亡,细胞内谷氨 (GSH) 水平和酶活性 (GR,SOD,GPx,CAT).
- 评估了细胞亡标记物 (P53),细胞循环调节物 (环林,CDK) 和AMPK,PGK1和PKM2的基因表达.
主要成果:
- 在A375细胞中,CEG治疗导致细胞循环停止 (G0/G1阶段) 和亡的增加.
- CEG显著抑制了PGK1和PKM2基因表达和酶活性,与AMPK,PGK1和PKM2具有强烈的in-silico结合亲缘关系.
- CEG降低了GSH水平和氧化应激酶的活性,同时降低了细胞循环调节者的下调和上调AMPK.
结论:
- 通过增强P53和抑制氧化应激和细胞循环酶,CEG会诱导A375黑色素瘤细胞的亡.
- CEG上调调节AMPK,下调调节PGK1和PKM2,通过癌细胞中的有氧糖解扰乱ATP生成.
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