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Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma

Tiziana Petrachi1, Alessandra Romagnani1, Adriana Albini2

  • 1Laboratory of Translational Research, Department of Scientific Direction, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.

Oncotarget
|December 31, 2016
PubMed

Insights

Phenformin effectively targets both cancer stem cells (CSCs) and non-CSC melanoma cells, reducing tumor viability and growth. This study suggests phenformin as a potential anti-cancer therapy for melanoma, impacting aggressive cell populations.

Area of Science:

  • Oncology
  • Metabolic pathways
  • Cancer stem cells

Background:

  • Melanoma is a treatment-resistant skin cancer driven by aggressive cancer stem cells (CSCs).
  • CSCs possess a distinct metabolic profile, making them a target for anti-cancer strategies.
  • Biguanides like metformin and phenformin alter cellular metabolism and show anti-cancer effects.

Purpose of the Study:

  • To investigate the efficacy of phenformin and metformin in targeting melanoma cancer stem cells.
  • To determine if phenformin affects melanoma cell viability, growth, and invasion.
  • To explore the impact of phenformin on CSC markers and survival factors.

Main Methods:

  • Utilized 2D and 3D (spheroid) melanoma models.
  • Assessed cell viability, growth, and invasion.
  • Measured expression of CSC markers and MITF levels.
  • Investigated phenformin's effects independently of SOX2 levels.

Main Results:

  • Phenformin significantly reduced melanoma cell viability, growth, and invasion, unlike metformin.
  • Phenformin decreased melanoma CSC markers and MITF levels.
  • Phenformin impacted both CSC (ALDHhigh) and non-CSC (ALDHlow) populations, reducing viable cells in spheroids.
  • Phenformin's effects were independent of SOX2 levels.

Conclusions:

  • Phenformin effectively targets both CSC and non-CSC melanoma cells.
  • Phenformin demonstrates potential as an anti-cancer therapeutic for melanoma by affecting cell viability and growth.
  • Targeting metabolic pathways in melanoma CSCs with phenformin warrants further investigation.
Keywords:
ALDHcancer stem cellsmelanomaphenformintherapy

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