Metformin inhibits melanoma development through autophagy and apoptosis mechanisms

被引:0
|
作者
T Tomic
T Botton
M Cerezo
G Robert
F Luciano
A Puissant
P Gounon
M Allegra
C Bertolotto
J-M Bereder
S Tartare-Deckert
P Bahadoran
P Auberger
R Ballotti
S Rocchi
机构
[1] INSERM U895,
[2] team 1,undefined
[3] Centre Méditerranéen de Médecine Moléculaire (C3 M),undefined
[4] équipe 1: Biologie et pathologies des cellules mélanocytaires,undefined
[5] Bâtiment Archimed,undefined
[6] Université de Nice Sophia Antipolis,undefined
[7] Faculté de Médecine,undefined
[8] IFR50,undefined
[9] INSERM,undefined
[10] U895,undefined
[11] équipe 2: Mort cellulaire,undefined
[12] différenciation et cancer,undefined
[13] Centre Commun de Microscopie Appliquée,undefined
[14] Faculté des Sciences,undefined
[15] Parc Valrose,undefined
[16] Centre Hospitalier Universitaire de Nice,undefined
[17] Hopital l’Archet,undefined
[18] Service de Dermatologie,undefined
[19] Centre Hospitalier Universitaire de Nice,undefined
[20] Hopital l’Archet,undefined
[21] Chirurgie générale et Cancérologie Digestive,undefined
来源
Cell Death & Disease | 2011年 / 2卷
关键词
melanoma; metformin; autophagy; apoptosis;
D O I
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学科分类号
摘要
Metformin is the most widely used antidiabetic drug because of its proven efficacy and limited secondary effects. Interestingly, recent studies have reported that metformin can block the growth of different tumor types. Here, we show that metformin exerts antiproliferative effects on melanoma cells, whereas normal human melanocytes are resistant to these metformin-induced effects. To better understand the basis of this antiproliferative effect of metformin in melanoma, we characterized the sequence of events underlying metformin action. We showed that 24 h metformin treatment induced a cell cycle arrest in G0/G1 phases, while after 72 h, melanoma cells underwent autophagy as demonstrated by electron microscopy, immunochemistry, and by quantification of the autolysosome-associated LC3 and Beclin1 proteins. In addition, 96 h post metformin treatment we observed robust apoptosis of melanoma cells. Interestingly, inhibition of autophagy by knocking down LC3 or ATG5 decreased the extent of apoptosis, and suppressed the antiproliferative effect of metformin on melanoma cells, suggesting that apoptosis is a consequence of autophagy. The relevance of these observations were confirmed in vivo, as we showed that metformin treatment impaired the melanoma tumor growth in mice, and induced autophagy and apoptosis markers. Taken together, our data suggest that metformin has an important impact on melanoma growth, and may therefore be beneficial in patients with melanoma.
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页码:e199 / e199
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