Apr 18, 2020

Topsentinol L Trisulfate, a new Marine Natural Product, that Targets Basal-like and Claudin-low Breast Cancers

BioRxiv : the Preprint Server for Biology
N. N. El-ChaarP. J. Moos

Abstract

Background: Breast cancer is a heterogeneous disease. Genomic studies have revealed five different intrinsic subtypes - Luminal A, Luminal B, HER2-enriched, Claudin-low, and Basal-like. Patients diagnosed with Basal-like or Claudin-low breast cancer (BL-CL) suffer from poor prognosis and limited treatment options. Hence, there is an urgent need to identify a new therapeutic lead that can benefit patients with BL-CL breast cancer. Methods: We used a step-wise screening approach to screen 2778 HP20 fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancer. We also performed biochemical investigations to study the effect of the compound in the signaling pathway. Finally, we generated a drug response gene-expression signature and projected it against a human tumor panel of 12 different cancer types to identify other cancer types sensitive to the compound. Results: We identified a previously unreported trisulfated sterol, topsentinol L trisulfate (TLT) that exhibits increased efficacy against BL-CL relative to Luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL revealed its ability to inhibit activation of AMPK and CHK1 and prom...Continue Reading

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Mentioned in this Paper

In Vivo
Crystal - Body Material
Patterns
Aquatic Organisms
Regulation of Biological Process
Peptide Hydrolases
Endopeptidases
Proteolytic Enzyme
Magnetospirillum magneticum
Omi serine protease

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