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Marizomib Promotes Senescence or Long-Term Apoptosis in Melanoma Cancer Cells

Wiktoria Monika Piskorz1, Rafał Krętowski1, Marzanna Cechowska-Pasko1

  • 1Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Mickiewicza 2A, 15-222 Białystok, Poland.

Molecules (Basel, Switzerland)
|December 17, 2024
PubMed

Insights

Marizomib (MZB), a proteasome inhibitor, induces cellular senescence in G361 melanoma cells and apoptosis in A375 melanoma cells. This suggests MZB

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Cellular senescence, a state of irreversible cell cycle arrest, is a key target for cancer therapy.
  • Inducing senescence followed by senolysis offers a novel approach to eliminate cancer cells.
  • The role of proteasome inhibitors in inducing senescence, particularly in malignant melanoma, remains underexplored.

Purpose of the Study:

  • To investigate the potential of marizomib (MZB), a natural proteasome inhibitor, to induce senescence or apoptosis in malignant melanoma cell lines.
  • To evaluate the effects of MZB treatment both during incubation and after its removal.

Main Methods:

  • Malignant melanoma cell lines (A375 and G361) were incubated with MZB.
  • Cellular senescence was assessed by SA-β-galactosidase staining and expression of P21, P-P53, and lamin B1.
  • Apoptosis was evaluated by cell cycle analysis (subG1, G2/M, S phases) and cleaved lamin B1 levels.

Main Results:

  • After 48 hours of MZB incubation, increased SA-β-galactosidase positive cells and upregulated P21/P-P53 were observed.
  • The G361 cell line showed increased subG1 phase, indicative of apoptosis, while A375 cells exhibited arrest in subG1 and G2/M phases.
  • Following MZB removal, G361 cells displayed senescence markers, whereas A375 cells showed increased apoptosis markers.

Conclusions:

  • Marizomib (MZB) effectively induces cellular senescence in G361 malignant melanoma cells.
  • MZB promotes apoptosis in A375 malignant melanoma cells.
  • MZB demonstrates potential as a therapeutic agent for malignant melanoma treatment.
Keywords:
NPI-0052apoptosiscancer treatmentproteasome inhibitionsalinosporamide Asenescence

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