Article ; Online: 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.
2021 Volume 19, Issue 5
Abstract: 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 ... ...
Abstract | 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. |
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MeSH term(s) | Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Culture Techniques ; Cell Line, Tumor ; Computational Biology ; Female ; Humans ; Protein Interaction Maps ; Proteome ; Proteomics ; Sesterterpenes/pharmacology ; Signal Transduction ; Spheroids, Cellular ; Time Factors ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology |
Chemical Substances | Antineoplastic Agents ; Proteome ; Sesterterpenes ; furospinosulin-1 |
Language | English |
Publishing date | 2021-04-28 |
Publishing country | Switzerland |
Document type | Comparative Study ; Journal Article |
ZDB-ID | 2175190-0 |
ISSN | 1660-3397 ; 1660-3397 |
ISSN (online) | 1660-3397 |
ISSN | 1660-3397 |
DOI | 10.3390/md19050249 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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