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Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

Song, Chang W ; Lee, Hyemi ; Dings, Ruud P M ; Williams, Brent ; Powers, John ; Santos, Troy Dos ; Choi, Bo-Hwa ; Park, Heon Joo

Scientific reports, 2012-04, Vol.2 (1), p.362-362, Article 362 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells
Autor: Song, Chang W ; Lee, Hyemi ; Dings, Ruud P M ; Williams, Brent ; Powers, John ; Santos, Troy Dos ; Choi, Bo-Hwa ; Park, Heon Joo
Assuntos: Adenylate Kinase - metabolism ; Animals ; Antidiabetics ; Antineoplastic Agents - pharmacology ; Breast cancer ; Cancer ; Cell proliferation ; Cell survival ; Cytotoxicity ; Death ; Diabetes mellitus ; Fibrosarcoma ; Humans ; Ionizing radiation ; Metformin ; Metformin - pharmacology ; Mice ; Mice, Inbred C3H ; Neoplasms - enzymology ; Neoplasms - metabolism ; Neoplasms - pathology ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - enzymology ; Neoplastic Stem Cells - metabolism ; Radiation-Sensitizing Agents - pharmacology ; Radiosensitivity ; Ribosomal Protein S6 Kinases - metabolism ; Signal transduction ; Stem cell transplantation ; Stem cells ; TOR protein ; TOR Serine-Threonine Kinases - metabolism ; Tumors
É parte de: Scientific reports, 2012-04, Vol.2 (1), p.362-362, Article 362
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, and significantly enhanced the radiation-induced growth delay of FSaII tumors (s.c.) in the legs of C3H mice. Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors. Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

Song, Chang W ; Lee, Hyemi ; Dings, Ruud P M ; Williams, Brent ; Powers, John ; Santos, Troy Dos ; Choi, Bo-Hwa ; Park, Heon Joo

England: Nature Publishing Group

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