Bulbine frutescens phytochemical inhibits notch signaling pathway and induces apoptosis in triple negative and luminal breast cancer cells

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dc.contributor.authorKushwaha P.P.
dc.contributor.authorVardhan P.S.
dc.contributor.authorKapewangolo P.
dc.contributor.authorShuaib M.
dc.contributor.authorPrajapati S.K.
dc.contributor.authorSingh A.K.
dc.contributor.authorKumar S.
dc.date.accessioned2020-01-31T11:33:54Z
dc.date.accessioned2024-08-13T10:34:47Z
dc.date.available2020-01-31T11:33:54Z
dc.date.available2024-08-13T10:34:47Z
dc.date.issued2019
dc.description.abstractBreast cancer (BCa) is the most commonly diagnosed lethal cancer in women worldwide. Notch signaling pathway is directly linked to BCa recurrence and aggressiveness. Natural remedies are becoming a prime choice to overcome against cancer due to lesser side effect and cost-effectiveness. Bulbine frutescens (Asphodelaceae), a traditional medicinal plant in South Africa possess bioactive flavonoids and terpenoids. Polar (methanol) and non-polar (hexane) B. frutescens plant extracts were prepared. GC–MS analysis revealed the differential presence of secondary metabolites in both methanolic and hexane extracts. We hereby first time evaluated the anticancer potential of B. frutescens methanolic and hexane extract in triple-negative and luminal BCa cells. B. frutescens extracts significantly decreased cell viability (IC50 4.8–28.4 μg/ml) and induced cell cycle arrest at G1 phase in MDA-MB-231 and T47D cells as confirmed by spectrophotometry and flow cytometry technique. RT-PCR analysis of cell cycle (cyclin D1, CDK4, and p21) and apoptosis modulating genes (caspase 3, Bcl2 and survivin) revealed upexpression of p21, and caspase 3, and down expression of cyclin D1, CDK4, Bcl2 and survivin genes in extract-treated BCa cells. Fluorescence spectrophotometry and confocal microscopy showed B. frutescens induced nuclear morphology and mitochondrial integrity disruption, and increased reactive oxygen species production in MDA-MB-231 and T47D cells. Flow cytometric apoptosis analysis of B. frutescens extracts treated MDA-MB-231 cells showed ≈13% increase in early apoptotic population in comparison to non-treated cells. Dual-Luciferase Reporter assay confirmed notch promoter inhibitory activity of B. frutescens extracts. Moreover, RTPCR analysis showed down regulation of notch responsive genes (Hes1 and Hey1) at transcription levels in extract-treated BCa cells. Western Blot analysis showed increased procaspase 3 protein expression in extract-treated BCa cells. In all the assays methanolic extract showed better anti-cancer properties. Literature-based identification of methanol soluble phytochemicals in B. frutescens and in silico docking study revealed Bulbineloneside D as a potent ϒ-secretase enzyme inhibitor. In comparison to standard notch inhibitor, lead phytochemical showed two additional hydrophobic interactions with Ala80 and Leu81 amino acids. In conclusion, B. frutescens phytochemicals have cell cycle arrest, ROS production, apoptosis induction, and mitochondria membrane potential disruption efficacy in breast cancer cells. B. frutescens phytochemicals have the ability to downregulate the notch signaling pathway in triple-negative and luminal breast cancer cells.en_US
dc.identifier.doi10.1016/j.lfs.2019.116783
dc.identifier.issn243205
dc.identifier.urihttp://10.2.3.109/handle/32116/2510
dc.identifier.urlhttps://www.sciencedirect.com/science/article/abs/pii/S0024320519307106
dc.language.isoenen_US
dc.publisherElsevier Inc.en_US
dc.subjectAnticanceren_US
dc.subjectApoptosisen_US
dc.subjectBreast canceren_US
dc.subjectBulbine frutescensen_US
dc.subjectNatural productsen_US
dc.subjectNotch signalingen_US
dc.titleBulbine frutescens phytochemical inhibits notch signaling pathway and induces apoptosis in triple negative and luminal breast cancer cellsen_US
dc.title.journalLife Sciencesen_US
dc.typeArticleen_US
dc.type.accesstypeClosed Accessen_US

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