In silico and in vitro studies on the anti-cancer activity of andrographolide targeting survivin in human breast cancer stem cells.

PloS One
Septelia Inawati WanandiSekar Arumsari

Abstract

Breast cancer stem cells (BCSCs) express high levels of the anti-apoptotic protein, survivin. This study aimed to discover a natural active compound with anti-cancer properties that targeted survivin in human breast cancer stem cells. From the seven examined compounds, andrographolide was selected as a lead compound through in silico molecular docking with survivin, caspase-9, and caspase-3. We found that the affinity between andrographolide and survivin is higher than that with caspase-9 and caspase-3. Human CD24-/CD44+ BCSCs were treated with andrographolide in vitro for 24 hours. The cytotoxic effect of andrographolide on BCSCs was compared to that on human mesenchymal stem cells (MSCs). The expression of survivin, caspase-9, and caspase-3 mRNA was analyzed using qRT-PCR, while Thr34-phosphorylated survivin and total survivin levels were determined using ELISA and Immunoblotting assay. Annexin-V/PI flow cytometry assays were performed to evaluate the apoptotic activity of andrographolide. Our results demonstrate that the CC50 of andrographolide in BCSCs was 0.32mM, whereas there was no cytotoxic effect in MSCs. Moreover, andrographolide decreased survivin and Thr34-phosphorylated survivin, thus inhibiting survivin activation...Continue Reading

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Datasets Mentioned

BETA
AAC51660

Methods Mentioned

BETA
PCR
ELISA
electrophoresis
flow cytometry
ubiquitination

Software Mentioned

MOE
FireDock ( Fast Interaction in Molecular Docking Refinement )
MMFF94x
PathScan
MODEL
ChemDraw Ultra
- Blast
Alpha Site Finder
SWISS
Primer

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