title: Adenomatous polyposis coli (APC)-induced apoptosis of HT29 colorectal cancer cells depends on mitochondrial oxidative metabolism.
abstract: Adenomatous polyposis coli (APC) is a tumor suppressor involved in the Wnt signaling, the primary driving force of the intestinal epithelium homeostasis. Alterations of components of the Wnt pathway, and in most cases mutations of APC, have been reported to promote colorectal cancer (CRC). During differentiation the enterocytes migrate from the crypt to the tip of the villus where they undergo apoptosis thus ensuring the continual renewal of the intestinal mucosa. The differentiation process is characterized by an activation gradient of the Wnt signaling pathway accompanied by a metabolic switch from glycolysis to mitochondrial oxidative phosphorylation along the crypt-villus axis. In the present work, we study the relationship between the expression of wild type APC protein and mitochondrial oxidative metabolism in HT29 colorectal cancer cells, originally carrying endogenous inactive APC alleles. By generating mtDNA-depleted (rho0) APC-inducible HT29 cells, we demonstrate for the first time that the APC-dependent apoptosis requires the production of reactive oxygen species (ROS) by the mitochondrial respiratory chain. The possible role of mitochondria as putative target in the prevention and/or therapy of colorectal cancer is herein discussed.
authors.affiliation: Institute for Research, Hospitalization, and Scientific Care, Istituto Oncologico Giovanni Paolo II, 70124 Bari, Italy; Laboratory of Lipid Metabolism and Cancer, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors.forename: Maricarmen
authors.initials: M
authors.lastname: Cristofaro
authors.affiliation: Laboratory of Lipid Metabolism and Cancer, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy; Unit of Molecular Pathology and Genomics, Center for Sciences on the Ageing CeSI, G. D'Annunzio University of Chieti-Pescara, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Contursi
authors.affiliation: Institute for Research, Hospitalization, and Scientific Care, Istituto Oncologico Giovanni Paolo II, 70124 Bari, Italy; Laboratory of Lipid Metabolism and Cancer, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: D'Amore
authors.affiliation: Laboratory of Lipid Metabolism and Cancer, Fondazione Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Martelli
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, 70124 Bari, Italy.
authors.forename: Ada Fiorenza
authors.initials: AF
authors.lastname: Spaziante
authors.affiliation: Institute for Research, Hospitalization, and Scientific Care, Istituto Oncologico Giovanni Paolo II, 70124 Bari, Italy; Clinica Medica Cesare Frugoni, Interdisciplinary Department of Medicine, University of Bari Aldo Moro, 70124 Bari, Italy. Electronic address: antonio.moschetta@uniba.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Moschetta
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, 70124 Bari, Italy. Electronic address: gaetano.villani@uniba.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Villani
keywords: Apoptosis; Colorectal cancer; Mitochondria; Reactive oxygen species (ROS); Respiratory chain; Wnt signaling