Cirsilineol inhibits proliferation of lung squamous cell carcinoma by inducing ROS mediated apoptosis. (September 2020)

• Record Type: Journal Article
• Authors: Pathak, Gauri; Singh, Shilpi; Kumari, Priyanka; Hussain, Yusuf; Raza, Waseem; Luqman, Suaib; Meena, Abha
• Is Part Of: Food and chemical toxicology. Volume 143(2020)
• Publication Date: 2020-09
• Subjects: Cirsilineol -- Lung cancer -- Apoptosis -- ROS -- Ornithine decarboxylase -- Cycloxygenase-2; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111550
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 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. Highlights: Cirsilineol showed a good binding affinity with different cancer biomarkers. Cirsilineol moderately inhibits ODC and COX-2 activity. Cirsilineol inhibit the proliferation of lung squamous carcinoma cell line. Cirsilineol-induces apoptosis by increasing sub-diploid population and intracellular ROS levels. Cirsilineol is non-toxic to primary peritoneal macrophages & non-mutagenic.