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Coordinate autophagy and translation inhibition enhance cell death in melanoma

Dorota Gil1, Marta Zarzycka2, Małgorzata Lekka3

  • 1Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland. dorotabeata.gil@uj.edu.pl.

Folia Medica Cracoviensia
|February 19, 2025
PubMed

Insights

Co-inhibiting autophagy and translation pathways with chloroquine and translation inhibitors like NVP-BEZ235 can overcome melanoma drug resistance. This combined approach induces apoptosis, suppressing melanoma growth and invasiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Targeted melanoma therapies face challenges with acquired drug resistance.
  • Autophagy and translation pathways are interconnected and play roles in cancer drug resistance.

Purpose of the Study:

  • To investigate the combined effect of inhibiting autophagy and translation pathways in melanoma.
  • To explore a novel therapeutic strategy for overcoming drug resistance in melanoma.

Main Methods:

  • Utilized chloroquine (autophagy inhibitor) combined with two translation inhibitors (NVP-BEZ235 and CGP57380).
  • Conducted studies on human melanoma cell lines with BRAFV600E and PTEN loss mutations.
  • Assessed cell invasiveness, growth, and apoptosis induction.

Main Results:

  • The drug combination suppressed melanoma cell invasiveness and growth.
  • Coordinated inhibition of translation and autophagy induced apoptosis in melanoma cells.
  • Demonstrated direct and indirect interactions between translation machinery and autophagy.

Conclusions:

  • Combined inhibition of translation and autophagy presents a potential therapeutic model for melanoma.
  • This strategy may overcome acquired drug resistance in malignant melanoma.
  • Promotes apoptosis, offering a new avenue for melanoma treatment.
Keywords:
MNKchloroquineeIF2αeIF4EmTORmelanoma

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