Scatena 2017 MITOEAGLE Obergurgl
Event: MitoEAGLE Obergurgl 2017
Recent data confirm that PPARγ-ligands, like metformin, may cause erosion of CML stem cell by inducing differentiation . Our previous data [2,3] showed that these antidiabetic drugs also inhibit the mitochondrial respiratory chain. The interrelationship among PPARs, mitochondria, and cell differentiation represents a topic with important experimental and clinical implications. In fact, by modulating neoplastic cell differentiation, it could be possible to identify cytodifferentiation-related protein expression changes that can be utilized as cancer biomarkers. Moreover, it permits us to better define the molecular basis related to this drug induced cancer cell and cancer stem cell differentiation to therapeutic purposes.
To this aim, we investigated ciglitazone-induced differentiation of a human hepatocarcinoma HepG2 cell line, by monitoring biochemical and cellular parameters of cytodifferentiation and modifications of cellular proteome through MS analysis. Moreover, mitochondrial respiration was analyzed by high-resolution respirometry.
Results indicated that ciglitazone is a differentiating agent for the HepG2 cell line. This process is associated with serious derangement of oxidative mitochondria metabolism and intriguing modifications of protein expression related to: Mitochondrial proteome; Metabolic Enzymes; Cell antioxidant system; Cell cycle ; Signal transduction pathways; Cellular stress; Invasiveness.
A careful definition of the complex pathophysiology of CSCs may have important direct and indirect implications in molecular and cellular biology of cancer. Moreover, the identification of a molecular phenotype for these pathogenically relevant cancer cells, associated to an accurate definition of their typical derangement in cell differentiation and, and above all, metabolism, can represent a fundamental advance in terms of early diagnosis and selective therapy of cancer. Last but not least, the knowledge of pathogenetic mechanisms at the basis of CSCs can enlarge and ameliorate the therapeutic applications of the normal adult stem.
Labels: MiParea: Pharmacology;toxicology Pathology: Cancer
Organism: Human Tissue;cell: Liver
Event: A1, Poster Metformin
- Inst Biochem Clinical Biochem, Catholic Univ, Rome, Italy.- [email protected]
- Prost S, Relouzat F, Spentchian M, Ouzegdouh Y, Saliba J, Massonnet G, Beressi JP, Verhoeyen E, Raggueneau V, Maneglier B, Castaigne S, Chomienne C, Chrétien S, Rousselot P, Leboulch P (2015) Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature 525:380-3.
- Bottoni P, Giardina B, Vitali A, Boninsegna A, Scatena R (2009) A proteomic approach to characterizing ciglitazone-induced cancer cell differentiation in Hep-G2 cell line. Biochim Biophys Acta 1794:615-26.
- Scatena R, Bottoni P, Martorana GE, Ferrari F, De Sole P, Rossi C, Giardina B (2004) Mitochondrial respiratory chain dysfunction, a non-receptor-mediated effect of synthetic PPAR-ligands: biochemical and pharmacological implications. Biochem Biophys Res Commun 319:967-73.