Cancer letters, 2019-07, Vol.455, p.60-72
2019
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- Autor(en) / Beteiligte
- Titel
- A novel hydrogen sulfide-releasing donor, HA-ADT, suppresses the growth of human breast cancer cells through inhibiting the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling pathways
- Ist Teil von
- Cancer letters, 2019-07, Vol.455, p.60-72
- Ort / Verlag
- Ireland: Elsevier B.V
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Breast cancer is one of the most frequent cancers among women worldwide. Hyaluronic acid (HA) is one of the best biopolymers in terms of safety issues and has been widely used in drug delivery and tissue engineering. 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH) is a commonly used H2S donor. In this study, we designed and synthesized a conjugate, HA-ADT, by connecting HA with ADT-OH through chemical reactions. Our results indicated that HA-ADT could produce more H2S than NaHS and GYY4137. HA-ADT exerted more potent inhibitory effects than NaHS and GYY4137 in the proliferation, viability, migration, and invasion of human breast cancer cells. Similar trends were observed in the apoptosis and the protein levels of phospho (p)-PI3K, p-AKT, p-mTOR, H-RAS, p-RAF, p-MEK, and p-ERK in human breast cancer cells. Furthermore, HA-ADT exhibited more powerful inhibitory effects on the growth of human breast cancer xenograft tumors in nude mice. In conclusion, HA-ADT could suppress the growth of human breast cancer cells through the inhibition of the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK signaling pathways. HA-ADT and its derivatives might be of great potential in the treatment of different types of cancer. •HA-ADT produces more H2S than NaHS and GYY4137.•HA-ADT decreases the proliferation and viability of human breast cancer cells.•HA-ADT suppresses the migration and invasion of human breast cancer cells.•HA-ADT induces apoptosis through PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways.•HA-ADT inhibits the growth and angiogenesis of human breast cancer xenografts.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0304-3835, 1872-7980eISSN: 1872-7980DOI: 10.1016/j.canlet.2019.04.031Titel-ID: cdi_proquest_miscellaneous_2219003397
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, AKT protein, Angiogenesis, Animals, Apoptosis, Biopolymers, Breast cancer, Breast Neoplasms - drug therapy, Breast Neoplasms - metabolism, Cancer therapies, Cell growth, Cell Growth Processes - drug effects, Cell Line, Tumor, Cell proliferation, Chemical reactions, Drug delivery, Enzyme Inhibitors - administration & dosage, Enzyme Inhibitors - chemistry, Enzyme Inhibitors - pharmacology, Extracellular signal-regulated kinase, Female, H-Ras protein, Humans, Hyaluronic acid, Hydrogen sulfide, Hydrogen Sulfide - administration & dosage, Hydrogen Sulfide - chemistry, MAP Kinase Kinase Kinases - antagonists & inhibitors, MAP Kinase Kinase Kinases - metabolism, MAP Kinase Signaling System - drug effects, MCF-7 Cells, Mice, Inbred BALB C, Molecular structure, NMR, Nuclear magnetic resonance, Penicillin, Phosphatidylinositol 3-Kinases - metabolism, Proteins, Proto-Oncogene Proteins c-akt - antagonists & inhibitors, raf Kinases - antagonists & inhibitors, raf Kinases - metabolism, Raf protein, ras Proteins - metabolism, Signal transduction, Signaling pathway, Tissue engineering, TOR protein, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - metabolism, Tumors, Viability, Xenografts