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Cirsilineol inhibits proliferation of lung squamous cell carcinoma by inducing ROS mediated apoptosis.
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2020-07-05 , DOI: 10.1016/j.fct.2020.111550
Gauri Pathak 1 , Shilpi Singh 1 , Priyanka Kumari 1 , Yusuf Hussain 1 , Waseem Raza 2 , Suaib Luqman 1 , Abha Meena 1
Affiliation  

Cirsilineol belonging to the flavones category have not been explored in detail for anti-proliferative potential, therefore selected for the investigation. Hence, the antiproliferative potential of cirsilineol has been established in NCIH-520 cells. Cirsilineol exhibited good binding-energy and inhibited the activity of ODC, CATD, DHFR, HYAL, LOX-5, and COX-2 up to 45.14% at 100 μM. It significantly inhibited the proliferation of NCIH-520 cells (81.96%) and likewise, the proliferation of other cell lines up to 48.50%. It also induced an increase in the sub-diploid cell population, which then leads to an increase in apoptosis by 2.64 and 5.12 fold at 10 μM and 100 μM respectively. Further, the Annexin-V-FITC assay confirmed the late apoptosis and necrosis in the NCIH-520 cell line induced by cirsilineol. The ROS production was enhanced by 1.16 and 2.22 folds at 10 μM and 100 μM respectively. Besides, cirsilineol revealed acceptable ADME properties, non-toxic and non-mutagenic compound. Altogether, these findings provide evidence that cirsilineol inhibited the proliferation of NCIH-520 cells by inducing ROS-mediated apoptosis and offer new insight into the anti-proliferative potential of cirsilineol, which can further be exploited to either synthesise new derivatives or its candid usage as a herbal lead for cancer treatment.



中文翻译:

Cirsilineol通过诱导ROS介导的凋亡来抑制肺鳞状细胞癌的增殖。

尚未对黄酮类中的西西林醇具有抗增殖潜力的详细研究,因此选择进行调查。因此,已在NCIH-520细胞中建立了西西里醇的抗增殖潜能。Cirsilineol表现出良好的结合能,并在100μM时抑制ODC,CATD,DHFR,HYAL,LOX-5和COX-2的活性高达45.14%。它显着抑制了NCIH-520细胞的增殖(81.96%),同样,其他细胞系的增殖也高达48.50%。它还诱导亚二倍体细胞群体的增加,然后导致凋亡在10μM和100μM时分别增加2.64和5.12倍。此外,膜联蛋白-V-FITC测定证实了由西西里醇诱导的NCIH-520细胞系中的晚期细胞凋亡和坏死。ROS产量提高了1。在10μM和100μM下分别为16和2.22倍。此外,西西里醇还显示出可接受的ADME性质,无毒且无致突变性的化合物。总而言之,这些发现提供了西西里醇通过诱导ROS介导的凋亡而抑制NCIH-520细胞增殖的证据,并为西西里醇的抗增殖潜力提供了新的见识,其可以进一步用于合成新的衍生物或作为其坦率的用途。一种用于治疗癌症的草药。

更新日期:2020-07-10
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