Effects of phenformin on the proliferation of human tumor cell lines.
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 microM) 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.
Caraci
Filippo
F
Department of Pharmaceutical Sciences, University of Catania, Catania, Italy.
Chisari
Mariangela
M
Frasca
Giuseppina
G
Chiechio
Santina
S
Salomone
Salvatore
S
Pinto
Antonio
A
Sortino
Maria Angela
MA
Bianchi
Alfredo
A
D000230:Adenocarcinoma / Q000473:pathology; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D009447:Neuroblastoma / Q000473:pathology; D015689:Oncogene Protein p21(ras) / Q000187:drug effects; D010629:Phenformin / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D003470:Culture Media; D007004:Hypoglycemic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D010629:Phenformin; D015689:Oncogene Protein p21(ras); C022616:thiazolyl blue; D005947:Glucose