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Mitochondrial apoptosis and curtailment of hypoxia-inducible factor-1α/fatty acid synthase: A dual edge perspective of gamma linolenic acid in ER+ mammary gland cancer.
Cell Biochemistry and Function ( IF 2.8 ) Pub Date : 2020-03-23 , DOI: 10.1002/cbf.3513
Subhadeep Roy 1 , Manjari Singh 1 , Atul Rawat 2 , Dinesh Kumar 2 , Gaurav Kaithwas 1
Affiliation  

Gamma linolenic acid is a polyunsaturated fatty acid having selective anti‐tumour properties with negligible systemic toxicity. In the present study, the anti‐cancer potential of gamma linolenic acid and its effects on mitochondrial as well as hypoxia‐associated marker was evaluated. The effect of gamma linolenic acid was scrutinised against ER + MCF‐7 cells by using fluorescence microscopy, JC‐1 staining, dot plot assay and cell cycle analysis. The in vitro results were also confirmed using carcinogen (n‐methyl‐n‐nitrosourea) induced in vivo model. The early and late apoptotic signals in the conjugation with mitochondrial depolarisation were found once scrutinised through mitochondrial membrane potential and life death staining after gamma linolenic acid treatment. Gamma linolenic acid arrested the cell cycle in G0/G1 phase with the majority of cell populations in the early apoptotic stage. The translocation of phosphatidylserine was studied through annexin‐V FITC dot plot assay. The markers of cellular proliferation (decreased alveolar bud count, histopathological architecture restoration and loss of tumour micro‐vessels) were diminished after gamma linolenic acid treatment. Gamma linolenic acid ameliorates the biological effects of n‐methyl‐n‐nitrosourea persuading the mitochondrial mediated death pathway and impeding the hypoxic microenvironment to make a halt in palmitic acid synthesis.

中文翻译:

线粒体凋亡和缺氧诱导因子-1α/脂肪酸合酶的削减:γ+亚麻酸在ER +乳腺癌中的双重视角。

γ-亚麻酸是一种多不饱和脂肪酸,具有选择性的抗肿瘤特性,全身毒性可忽略不计。在本研究中,评估了γ-亚麻酸的抗癌潜力及其对线粒体及缺氧相关标志物的影响。通过使用荧光显微镜,JC-1染色,斑点图分析和细胞周期分析,仔细检查了γ-亚麻酸对ER + MCF-7细胞的作用。的体外结果采用致癌物质(N-甲基-N-亚硝基脲)诱导也证实在体内模型。通过γ-亚麻酸处理后,通过线粒体膜电位和生命死亡染色仔细检查,发现与线粒体去极化结合的早期和晚期凋亡信号。γ亚麻酸将细胞周期阻滞在G0 / G1期,大部分细胞群处于凋亡早期。磷脂酰丝氨酸的易位通过膜联蛋白-V FITC点图分析法进行了研究。γ亚麻酸处理后,细胞增殖的标志物(肺泡芽数减少,组织病理学结构恢复和肿瘤微血管丢失)减少。
更新日期:2020-03-23
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