Cytotoxic evaluation of YSL-109 in a triple negative breast cancer cell line and toxicological evaluations DOI
Yudibeth Sixto‐López, Cynthia Ordaz‐Pichardo, José A. Gómez-Vidal

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2023, Volume and Issue: 396(6), P. 1211 - 1222

Published: Jan. 25, 2023

Language: Английский

Selective HDAC3 Inhibitors with Potent In Vivo Antitumor Efficacy against Triple-Negative Breast Cancer DOI
Sravani Pulya,

Ambati Himaja,

Milan Paul

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(17), P. 12033 - 12058

Published: Sept. 3, 2023

HDAC3 modulation shows promise for breast cancer, including triple-negative cases. Novel pyrazino-hydrazide-based inhibitors were designed and synthesized. Lead compound 4i exhibited potent inhibition (IC50 = 14 nM) with at least 121-fold selectivity. It demonstrated strong cytotoxicity against cancer cells (IC50: 0.55 μM 4T1, 0.74 MDA-MB-231) normal cell toxicity. Metabolically stable displayed a superior pharmacokinetic profile. A dose-dependent therapeutic efficacy of was observed in tumor-bearing mouse model. The biomarker analysis tumor tissues enhanced acetylation on Ac-H3K9, Ac-H3K27, Ac-H4K12 compared to Ac-tubulin Ac-SMC3 indicating selectivity vivo. immunoblotting study tissue showed upregulation apoptotic proteins caspase-3, caspase-7, cytochrome c the downregulation proliferation markers Bcl-2, CD44, EGFR, Ki-67. Compound represents promising candidate targeted therapy, particularly cases cancer.

Language: Английский

Citations

30
Inhibition of cancer cells by Quinoline-Based compounds: A review with mechanistic insights DOI
Anjali Saxena, Suman Majee, Devalina Ray

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 103, P. 117681 - 117681

Published: March 12, 2024

Language: Английский

Citations

15
Apigenin and its combination with Vorinostat induces apoptotic-mediated cell death in TNBC by modulating the epigenetic and apoptotic regulators and related miRNAs DOI Creative Commons

Snehal Nimal,

Navanath Kumbhar,

Saruchi

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 25, 2024

Triple-negative breast cancer (TNBC) is a metastatic disease and formidable treatment challenge as it does not respond to existing therapies. Epigenetic regulators play crucial role in the progression metastasis by modulating expression of anti-apoptotic, pro-apoptotic markers related miRNAs TNBC cells. We have investigated anti-TNBC potential dietary flavonoid 'Apigenin' its combination with Vorinostat on MDA-MB-231 At Apigenin generated ROS, inhibited cell migration, arrested cycle at subG0/G1 phases, induced apoptotic-mediated death. reduced class-I HDACs transcriptomic proteomic levels. In immunoblotting study, has upregulated downregulated anti-apoptotic proteins. enzymatic activity HDAC/DNMT increased HAT activity. manifested effect miRNA upregulating tumor-suppressor miR-200b downregulation oncomiR-21. Combination study growth cells synergistically epigenetic apoptotic regulators. Molecular docking MD simulations explored mechanism catalytic inhibition HDAC1 HDAC3 supported in-vitro studies. The overall studies demonstrated an may help design effective strategy treat phenotype TNBC.

Language: Английский

Citations

14
Emerging therapeutic strategies in cancer therapy by HDAC inhibition as the chemotherapeutic potent and epigenetic regulator DOI

Dipanjan Karati,

Swarupananda Mukherjee, Souvik Roy

et al.

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(4)

Published: March 5, 2024

Language: Английский

Citations

11
Unveiling Epigenetic Vulnerabilities in Triple-Negative Breast Cancer through 3D Organoid Drug Screening DOI Creative Commons
Xinxin Rao,

Zhibin Qiao,

Yang Yang

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 225 - 225

Published: Feb. 8, 2024

Triple-negative breast cancer (TNBC) poses a therapeutic challenge due to its aggressive nature and lack of targeted therapies. Epigenetic modifications contribute TNBC tumorigenesis drug resistance, offering potential targets. Recent advancements in three-dimensional (3D) organoid cultures, enabling precise screening, hold immense promise for identifying novel compounds targeting TNBC. In this study, we established two patient-derived organoids implemented high-throughput screening system using these cell lines. Screening library 169 epigenetic compounds, found that organoid-based systems offer remarkable precision response assessment compared cell-based models. The top 30 showing the highest sensitivity initial were further assessed secondary screen. Four panobinostat, pacritinib, TAK-901, JIB-04, histone deacetylase, JAK/STAT, demethylases, aurora kinase pathways, respectively, exhibited potent anti-tumor activity organoids, surpassing effect paclitaxel. Our study highlights drugs as effective agents demonstrates valuable role advancing discovery.

Language: Английский

Citations

7
Design and synthesis of pyridine-based benzamides as potent HDAC3 inhibitors as an armament against breast cancer with in vivo validation DOI

Ambati Himaja,

Ganesh Routholla,

Tarun Patel

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 291, P. 117636 - 117636

Published: April 17, 2025

Language: Английский

Citations

0
A promising future for breast cancer therapy with hydroxamic acid-based histone deacetylase inhibitors DOI

Tanima Das,

Sunandita Bhar,

Diya Ghosh

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108169 - 108169

Published: Jan. 20, 2025

Language: Английский

Citations

0
Comprehensive characterization of fatty acid oxidation in triple-negative breast cancer: Focus on biological roles and drug modulation DOI

Yunduo Liu,

Yanxia Zhang, Qin Xiang

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177343 - 177343

Published: Feb. 1, 2025

Language: Английский

Citations

0
Epigenetic Alterations in Cancer: The Therapeutic Potential of Epigenetic Drugs in Cancer Therapy DOI Creative Commons
Preeti Gupta

Drugs and Drug Candidates, Journal Year: 2025, Volume and Issue: 4(2), P. 15 - 15

Published: April 5, 2025

To date, numerous studies have emerged that indicate the possible role of epigenetic modulation in development and progression several diseases, including cancer. Epigenetic alterations participate various steps carcinogenesis. They play important regulatory roles processes like cell division, proliferation, angiogenesis, metastasis. Thus, modifications such as DNA methylation, histone modifications, non-coding RNAs serve attractive promising targets for cancer prevention anti-cancer therapy. drugs or epi-drugs possess ability to reverse many thus can help manage clinical manifestations broadly target methylation post-translational manifest their effects. Several naturally occurring well chemically synthesized compounds been recognized drugs. Some them are clinically approved, while preclinical trials. In this review, we aim present a broad overview implicated The review also compiles approved practice, those stages investigation

Language: Английский

Citations

0
Cyclin-dependent kinase 4 and 6 inhibitors in breast cancer treatment DOI

Zhengfei Guo,

Rui Dong, Y. Wu

et al.

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Language: Английский

Citations

0