Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway.

Anti-cancer Agents in Medicinal Chemistry
Imran KhanIrfan A Ansari

Abstract

Recently, the Notch signaling pathway has gained attention as a potential therapeutic target for chemotherapeutic intervention. However, the efficacy of previously known Notch inhibitors in colon cancer is still unclear. The purpose of this study was to investigate the effect of andrographolide on aberrantly activated Notch signaling in SW-480 cells in vitro. The cytostatic potential of andrographolide on SW-480 cells was evaluated by 3-(4,5-dimethylthiazol- 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, morphology assessment, and colony formation assay. The apoptotic activity was evaluated by FITC Annexin V assay, 4',6-diamidino-2-phenylindole (DAPI), Hoechst, Rhodamine 123, and Mito Tracker CMXRos staining. Scratch assay was conducted for migratory potential assessment. 7'-Dichlorodihydrofluorescein Diacetate (DCFH-DA) staining was used to evaluate the Reactive Oxygen Species (ROS) generation. Relative mRNA expression of Bax, Bcl2, NOTCH 1, and JAGGED 1 was estimated by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Cell cycle phase distribution was evaluated by Annexin V-FITC/PI staining. MTT assay demonstrated the dose and time-dependent cytotoxicity of andrographolide on SW-480 cells. It also inhibited t...Continue Reading

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