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Augmentation of danusertib's anticancer activity against melanoma by blockage of autophagy

Yuan-Yuan Shang1, Nan Yu1, Li Xia1

  • 1Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, 750004, People's Republic of China.

Drug Delivery and Translational Research
|October 19, 2019
PubMed

Insights

Danusertib inhibits melanoma growth by inducing apoptosis and cell cycle arrest. Blocking the autophagy induced by danusertib enhances its anticancer effects, suggesting a new therapeutic strategy for melanoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Aurora kinase is a key target in melanoma treatment.
  • Danusertib, an aurora kinase inhibitor, induces autophagy in various cancers.
  • Autophagy has a dual role in cancer, acting as both a pro-survival and anti-survival mechanism.

Purpose of the Study:

  • To investigate the role of danusertib in inducing autophagy in melanoma.
  • To determine the impact of danusertib-induced autophagy on its anticancer activity against melanoma.

Main Methods:

  • Investigated danusertib's effect on melanoma cell growth, cell cycle, and apoptosis.
  • Analyzed the inhibition of the Akt/mTOR signaling pathway and induction of autophagy by danusertib.
  • Assessed the impact of autophagy inhibition on danusertib's efficacy in melanoma.

Main Results:

  • Danusertib significantly inhibited melanoma growth by inducing cell cycle arrest and apoptosis.
  • Danusertib treatment inhibited the Akt/mTOR pathway and induced autophagy in melanoma cells.
  • Inhibiting autophagy enhanced danusertib's inhibitory effects on melanoma growth.

Conclusions:

  • Danusertib-induced autophagy acts as a survival mechanism in melanoma cells, potentially counteracting its anticancer effects.
  • Blocking autophagy can enhance the efficacy of danusertib as a melanoma therapy.
  • Targeting autophagy in combination with danusertib presents a novel strategy for melanoma treatment.
Keywords:
Akt/mTORAurora kinaseAutophagyDanusertibMelanoma

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