In:
PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 11 ( 2020-11-19), p. e0240020-
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 CC 50 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 and increasing survivin mRNA in BCSCs. The apoptotic activity of andrographolide was revealed by the increase of caspase-3 mRNA and protein, as well as the increase in both the early and late phases of apoptosis. In conclusion, andrographolide can be considered an anti-cancer compound that targets BCSCs due to its molecular interactions with survivin, caspase-9, and caspase-3, which induce apoptosis. We suggest that the binding of andrographolide to survivin is a critical aspect of the effect of andrographolide.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0240020
DOI:
10.1371/journal.pone.0240020.g001
DOI:
10.1371/journal.pone.0240020.g002
DOI:
10.1371/journal.pone.0240020.g003
DOI:
10.1371/journal.pone.0240020.g004
DOI:
10.1371/journal.pone.0240020.g005
DOI:
10.1371/journal.pone.0240020.g006
DOI:
10.1371/journal.pone.0240020.g007
DOI:
10.1371/journal.pone.0240020.t001
DOI:
10.1371/journal.pone.0240020.t002
DOI:
10.1371/journal.pone.0240020.t003
DOI:
10.1371/journal.pone.0240020.t004
DOI:
10.1371/journal.pone.0240020.t005
DOI:
10.1371/journal.pone.0240020.t006
DOI:
10.1371/journal.pone.0240020.s001
DOI:
10.1371/journal.pone.0240020.s002
DOI:
10.1371/journal.pone.0240020.s003
DOI:
10.1371/journal.pone.0240020.s004
DOI:
10.1371/journal.pone.0240020.s005
DOI:
10.1371/journal.pone.0240020.s006
DOI:
10.1371/journal.pone.0240020.s007
DOI:
10.1371/journal.pone.0240020.s008
DOI:
10.1371/journal.pone.0240020.s009
DOI:
10.1371/journal.pone.0240020.s010
DOI:
10.1371/journal.pone.0240020.s011
DOI:
10.1371/journal.pone.0240020.s012
DOI:
10.1371/journal.pone.0240020.s013
DOI:
10.1371/journal.pone.0240020.s014
DOI:
10.1371/journal.pone.0240020.s015
DOI:
10.1371/journal.pone.0240020.s016
DOI:
10.1371/journal.pone.0240020.r001
DOI:
10.1371/journal.pone.0240020.r002
DOI:
10.1371/journal.pone.0240020.r003
DOI:
10.1371/journal.pone.0240020.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2267670-3
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