Effects of phenformin on the proliferation of human tumor cell lines

Filippo Caraci, Mariangela Chisari, Giuseppina Frasca, Santina Chiechio, Salvatore Salomone, Antonio Pinto, Maria Angela Sortino, Alfredo Bianchi

Research output: Contribution to journalArticle

Abstract

Phenformin is a biguanide that has been largely used in the past for its anti-diabetic activity. A large body of evidence suggests additional effects of phenformin including antitumoral activity in different animal models in vivo. Thus, the present study has been conducted in order to elucidate possible mechanisms involved in the antitumoral effects of phenformin. In various tumoral cell lines (SH-SY5Y neuroblastoma and LNCaP prostate adenocarcinoma cells), increasing concentrations of phenformin (50-500 μM) induced a concentration-dependent inhibition of cell proliferation. This effect was not dependent on the ability of the drug to reduce glucose levels and was accompanied by induction of apoptotic cell death as measured by cytofluorometric analysis. In addition, a short-time incubation of SH-SY5Y cells with phenformin induced enhanced and transient expression of the cell cycle inhibitor p21 suggesting that phenformin causes inhibition of cell cycle progression prior to induction of apoptosis. These results demonstrate an activity at the cellular level of phenformin that supports its antitumoral effect observed in vivo.

Original languageEnglish
Pages (from-to)643-650
Number of pages8
JournalLife Sciences
Volume74
Issue number5
DOIs
Publication statusPublished - Dec 19 2003

Keywords

  • Apoptosis
  • Cell cycle
  • Cell growth
  • Toxicity

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Caraci, F., Chisari, M., Frasca, G., Chiechio, S., Salomone, S., Pinto, A., Sortino, M. A., & Bianchi, A. (2003). Effects of phenformin on the proliferation of human tumor cell lines. Life Sciences, 74(5), 643-650. https://doi.org/10.1016/j.lfs.2003.07.015