» Articles » PMID: 36694011

Cytotoxic Evaluation of YSL-109 in a Triple Negative Breast Cancer Cell Line and Toxicological Evaluations

Overview
Specialty Pharmacology
Date 2023 Jan 24
PMID 36694011
Authors
Affiliations
Soon will be listed here.
Abstract

Breast cancer (BC) is the leading cause of cancer-related death in women worldwide. Triple negative breast cancer (TNBC) is the most aggressive form of BC being with the worst prognosis and the worst survival rates. There is no specific pharmacological target for the treatment of TNBC; conventional therapy includes the use of non-specific chemotherapy that generally has a poor prognosis. Therefore, the search of effective therapies against to TNBC continues at both preclinical and clinical level. In this sense, the exploration of different pharmacological targets is a continue task that pave the way to epigenetic modulation using novel small molecules. Lately, the inhibition of histone deacetylases (HDACs) has been explored to treat different BC, including TNBC. HDACs remove the acetyl groups from the ɛ-amino lysine resides on histone and non-histone proteins. In particular, the inhibition of HDAC6 has been suggested to be useful for the treatment of TNBC due to it is overexpressed in TNBC. Therefore, in this work, an HDAC6 selective inhibitor, the (S)-4-butyl-N-(1-(hydroxyamino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl) benzamide (YSL-109), was assayed on TNBC cell line (MDA-MB231) showing an antiproliferative activity (IC = 50.34 ± 1.11 µM), whereas on fibroblast, it was lesser toxic. After corroborating the in vitro antiproliferative activity of YSL-109 in TNBC, the toxicological profile was explored using combined approach with in silico tools and experimental assays. YSL-109 shows moderate mutagenic activity on TA-98 strain at 30 and 100 µM in the Ames test, whereas YSL-109 did not show in vivo genotoxicity and its oral acute toxicity (LD) in CD-1 female mice was higher than 2000 mg/kg, which is in agreement with our in silico predictions. According to these results, YSL-109 represents an interesting compound to be explored for the treatment of TNBC under preclinical in vivo models.

Citing Articles

Small molecule agents for triple negative breast cancer: Current status and future prospects.

Ou Y, Wang M, Xu Q, Sun B, Jia Y Transl Oncol. 2024; 41:101893.

PMID: 38290250 PMC: 10840364. DOI: 10.1016/j.tranon.2024.101893.

References
1.
Al-Hamamah M, Alotaibi M, Ahmad S, Ansari M, Attia M, Nadeem A . Genetic and epigenetic alterations induced by the small-molecule panobinostat: A mechanistic study at the chromosome and gene levels. DNA Repair (Amst). 2019; 78:70-80. DOI: 10.1016/j.dnarep.2019.03.008. View

2.
Almansour N . Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence. Front Mol Biosci. 2022; 9:836417. PMC: 8824427. DOI: 10.3389/fmolb.2022.836417. View

3.
Al-Thoubaity F . Molecular classification of breast cancer: A retrospective cohort study. Ann Med Surg (Lond). 2020; 49:44-48. PMC: 6926136. DOI: 10.1016/j.amsu.2019.11.021. View

4.
Ames B, Durston W, Yamasaki E, Lee F . Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci U S A. 1973; 70(8):2281-5. PMC: 433718. DOI: 10.1073/pnas.70.8.2281. View

5.
Banerjee P, Eckert A, Schrey A, Preissner R . ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018; 46(W1):W257-W263. PMC: 6031011. DOI: 10.1093/nar/gky318. View