Back to Search
Start Over
Augmentation of danusertib’s anticancer activity against melanoma by blockage of autophagy
- Source :
- Drug Delivery and Translational Research. 10:136-145
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Previous evidence has shown that the increased expression of aurora kinase is closely related to melanoma progression and is an important therapeutic target in melanoma. Danusertib is an inhibitor of aurora kinase, and recent studies have shown that danusertib treatment induces autophagy in several types of cancer. Interestingly, autophagy plays a dual function in cancer as a pro-survival and anti-survival factor. In this study, we investigated the role of danusertib on the induction of autophagy in melanoma and determined the impact of autophagy induction on its anticancer activity against melanoma. Our results showed that danusertib can significantly inhibit melanoma growth by inducing cell cycle arrest and apoptosis. In addition, we demonstrated that danusertib treatment significantly inhibits the oncogenic Akt/mTOR signaling pathway and induces autophagy in melanoma cells. Furthermore, we identified that the inhibition of autophagy can enhance the inhibitory effects of danusertib on melanoma growth. Thus, the induction of autophagy by danusertib appears to be a survival mechanism in melanoma cells that may counteract its anticancer effects. These findings suggest a novel strategy to enhance the anticancer efficacy of danusertib in melanoma by blocking autophagy.
- Subjects :
- Cell cycle checkpoint
Cell Survival
Pharmaceutical Science
02 engineering and technology
030226 pharmacology & pharmacy
Mice
03 medical and health sciences
0302 clinical medicine
Aurora kinase
Cell Line, Tumor
Autophagy
medicine
Animals
Humans
Danusertib
Melanoma
Protein Kinase Inhibitors
neoplasms
Protein kinase B
Cell Proliferation
Chemistry
TOR Serine-Threonine Kinases
Cell Cycle
Cancer
Chloroquine
Drug Synergism
021001 nanoscience & nanotechnology
medicine.disease
Xenograft Model Antitumor Assays
Apoptosis
Benzamides
Cancer research
Pyrazoles
Female
0210 nano-technology
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 21903948 and 2190393X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Drug Delivery and Translational Research
- Accession number :
- edsair.doi.dedup.....fdd291eb62f9395a9b0e2a0720895244