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

Esther A Guzmán,Priscilla L Winder,Tara P Pitts,Amy E Wright

doi:10.3390/md19050249

Esther A Guzmán, Priscilla L Winder + Show 2 more

Open Access

https://doi.org/10.3390/md19050249

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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.

Highlights

The American Cancer Society estimates that 284,200 people (~1% patients are males) will be diagnosed with breast cancer in 2021, with an estimated 44,130 deaths expected from this disease [1]
This article reports the novel activity of furospinulosin 1 to selectively target MDA-MB231 TNBC cells only when they are grown as spheroids
While the compound was tested in two TNBC cell lines, it was only selected as a hit against the more stem-cell-like cell line MDA-MB-231 rather than the basal line MDA-MB-468

Summary

Introduction

The American Cancer Society estimates that 284,200 people (~1% patients are males) will be diagnosed with breast cancer in 2021, with an estimated 44,130 deaths expected from this disease [1]. A high incidence of triple negative breast cancer has been found in Mexican women; in this population, about 25% of those diagnosed with TNBC carry a BRCA1 mutation [2]. Triple negative breast cancers can aggressively spread to other organs, the brain and the lungs [3], and are more likely to recur than other breast cancers [4]. They are labeled as high-grade tumors because the cells bear very little resemblance to normal cells [3,4]

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