Singh Manjari, Devi Uma, Roy Subhadeep, Gupta Pushpraj S, Kaithwas Gaurav
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University) Vidya Vihar, Raebareli Road Lucknow-226025 UP India
Department of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, Sam Higginbottom University of Agricultural Sciences and Technology Naini Allahabad UP India.
RSC Adv. 2018 Apr 4;8(23):12848-12860. doi: 10.1039/c8ra01239c. eCollection 2018 Apr 3.
(4-[7-(Acetyloxy)-2-ethyl-2-chromen-3-yl] phenyl acetate) (BBAP-1) was identified as a potential prolyl hydroxylase-2 activator and tested for this activity using the 2-oxoglutarate dependent assay. BBAP-1 was evaluated for its cytotoxic potential against ER + MCF-7 cells, and -methyl--nitrosourea induced estrogen positive mammary gland carcinoma model. The effect of BBAP-1 on cellular morphology was evaluated using acridine orange/ethidium bromide and JC-1 staining. The morphological symptoms of apoptosis were evident after BBAP-1 treatment when studied through cell staining using acridine orange/ethidium bromide and JC-1 dye. Flow cytometric analysis revealed that BBAP-1 treatment arrested the cell cycle in the G2/M phase. study revealed the morphological changes of mammary gland tissue when scrutinized using carmine staining, hematoxylin and eosin staining and scanning electron microscopy. BBAP-1 treatment produced a marked effect on histopathological and morphological features when scrutinized against -methyl--nitrosourea induced mammary gland carcinoma. Treatment with BBAP-1 also attenuated the deleterious effects of -methyl--nitrosourea as measured on the basis of oxidative stress markers. Immunoblotting and qRT-PCR analysis revealed the participation of BBAP-1 in the mitochondrial mediated death apoptosis pathway and BBAP-1 also downregulated the hypoxic pathway through activation of prolyl hydroxylase-2. It was concluded that BBAP-1 activated the prolyl hydroxylase-2 enzyme and curtailed the over expression of hypoxia inducible factor-1α and fatty acid synthase along with the mitochondrial mediated death apoptosis pathway.
（4-[7-(乙酰氧基)-2-乙基-2-色原烯-3-基]苯基乙酸酯）（BBAP-1）被鉴定为一种潜在的脯氨酰羟化酶-2激活剂，并使用依赖于2-氧代戊二酸的测定法对其该活性进行了测试。对BBAP-1针对雌激素受体阳性（ER+）MCF-7细胞以及N-甲基-N-亚硝基脲诱导的雌激素阳性乳腺癌模型的细胞毒性潜力进行了评估。使用吖啶橙/溴化乙锭和JC-1染色评估了BBAP-1对细胞形态的影响。当通过使用吖啶橙/溴化乙锭和JC-1染料进行细胞染色研究时，BBAP-1处理后凋亡的形态学症状明显。流式细胞术分析显示，BBAP-1处理使细胞周期停滞在G2/M期。一项研究揭示了在使用胭脂红染色、苏木精和伊红染色以及扫描电子显微镜检查时乳腺组织的形态学变化。当针对N-甲基-N-亚硝基脲诱导的乳腺癌进行检查时，BBAP-1处理对组织病理学和形态学特征产生了显著影响。基于氧化应激标志物的测量，BBAP-1处理还减轻了N-甲基-N-亚硝基脲的有害影响。免疫印迹和qRT-PCR分析揭示了BBAP-1参与线粒体介导的死亡凋亡途径并且BBAP-1还通过激活脯氨酰羟化酶-2下调了缺氧途径。得出的结论是，BBAP-1激活了脯氨酰羟化酶-2酶，并减少了缺氧诱导因子-1α和脂肪酸合酶的过度表达以及线粒体介导的死亡凋亡途径。
