The Marine Natural Product Furospinulosin 1 Induces Apoptosis in MDA-MB-231 Triple Negative Breast Cancer Cell Spheroids, But Not in Cells Grown Traditionally with Longer Treatment

Cancer cells grown in spheroid conditions interact with each other and the extracellular matrix, providing a better representation of the in vivo environment than two-dimensional cultures and are a more clinically relevant model. A discrete screening of genetically diverse marine samples in the sphe...

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Bibliographic Details
Published in:Marine drugs 2021-04, Vol.19 (5), p.249
Main Authors: Guzmán, Esther A, Pitts, Tara P, Winder, Priscilla L, Wright, Amy E
Format: Article
Language:English
Subjects:
Apoptosis
Biocompatibility
Breast cancer
Cancer
Cancer therapies
Cell culture
Cells
Chemical compounds
Clinical trials
Cytotoxicity
Extracellular
Extracellular matrix
furospinulosin 1
Genetic screening
high content imaging
marine natural products
MEK inhibitors
Mutation
Natural products
Pharmacology
Protein arrays
Proteins
Selectivity
Spheroids
Toxicity
triple negative breast cancer
Tumors
Two dimensional models
Womens health
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Summary:Cancer cells grown in spheroid conditions interact with each other and the extracellular matrix, providing a better representation of the in vivo environment than two-dimensional cultures and are a more clinically relevant model. A discrete screening of genetically diverse marine samples in the spheroid assay led to the identification of a novel activity for the known compound furospinulosin 1. This compound shows activity against MDA-MB-231 triple negative breast cancer cells grown as spheroids and treated for 24 or 48 h. No cytotoxicity was seen in traditional two-dimensional adherent cultures treated for a longer time (72 h). A reverse phase protein array (RPPA) confirmed the limited activity of the compound in cells grown traditionally and revealed changes in protein expression when cells are grown as spheroids that are associated with better clinical prognosis. Analysis of the RPPA data through the Broad institute's connectivity map suggested the hypothesis that furospinulosin 1 functions as an MEK inhibitor. Analysis of the RPPA data through STRING supports the apoptosis observed. The selectivity exhibited by furospinulosin 1 for triple negative breast cancer cells only when grown as spheroids makes it an interesting compound with strong therapeutic potential that merits further study.
ISSN:1660-3397
1660-3397
DOI:10.3390/md19050249