Michela Illiano1, Ersilia Nigro2, Luigi Sapio1, Ilaria Caiafa1, Annamaria Spina1, Olga Scudiero3, Andrea Bianco4, Sabrina Esposito5, Filomena Mazzeo6, Paolo Vincenzo Pedone5, Aurora Daniele7, Silvio Naviglio1. 1. Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", Medical School, Via L. De Crecchio 7, 80138 Naples, Italy. 2. Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, University of Campania "Luigi Vanvitelli", Via G. Vivaldi 42, 81100 Caserta, Italy; CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy. 3. CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy. 4. Dipartimento di Scienze Cardio-Toraciche e Respiratorie, University of Campania "Luigi Vanvitelli", Via L. Bianchi, 80131, Napoli, Italy. 5. Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, University of Campania "Luigi Vanvitelli", Via G. Vivaldi 42, 81100 Caserta, Italy. 6. Dipartimento di Scienze e Tecnologie, Università di Napoli Partenope, Napoli, Italy. 7. Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, University of Campania "Luigi Vanvitelli", Via G. Vivaldi 42, 81100 Caserta, Italy; CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy. Electronic address: aurora.daniele@unina2.it.
Abstract
INTRODUCTION: Adipokines are known to play a relevant role in a number of cancer related molecular pathways. Adiponectin is a major adipokine with anti-inflammatory and beneficial metabolic actions. Furthermore, it has been shown to exert anti-carcinogenic effects in various tumor models and some clinical studies suggested an inverse relationship between circulating levels of adiponectin and an increased risk for development of malignancies. On the other hand, the cyclic AMP response element binding (CREB) transcription factor has been clearly linked to lung cancer. METHODS: we analyzed cell proliferation, cell cycle of A549 cells treated with adiponectin as well as CREB activation status in human lung adenocarcinoma A549 cells and in non-small cell lung cancer (NSCLC) samples. RESULTS: adiponectin treatment, at concentrations ranging between 5 and 50 μg/ml mimicking human serum levels, has a significant effect on reducing tumor cell proliferation of A549 cells, mainly by altering cell cycle progression. Importantly, we provide evidence that adiponectin clearly inhibits in a dose- and time-dependent manner CREB phosphorylation (activation) and, at least in part, also the level of CREB protein itself, preceding and accompanying the anti-proliferative effects in response to adiponectin. Moreover, in agreement with previous studies demonstrating that CREB over-expression occurs in many tumors, we also show by western-blotting from lung specimen that CREB is significantly up-regulated in NSCLC samples compared to adjacent normal tissues from six patients. CONCLUSIONS: Overall, our results represent the first evidence of CREB inhibition by adiponectin and may provide new insight into therapeutic strategies for lung cancer.
INTRODUCTION: Adipokines are known to play a relevant role in a number of cancer related molecular pathways. Adiponectin is a major adipokine with anti-inflammatory and beneficial metabolic actions. Furthermore, it has been shown to exert anti-carcinogenic effects in various tumor models and some clinical studies suggested an inverse relationship between circulating levels of adiponectin and an increased risk for development of malignancies. On the other hand, the cyclic AMP response element binding (CREB) transcription factor has been clearly linked to lung cancer. METHODS: we analyzed cell proliferation, cell cycle of A549 cells treated with adiponectin as well as CREB activation status in humanlung adenocarcinoma A549 cells and in non-small cell lung cancer (NSCLC) samples. RESULTS:adiponectin treatment, at concentrations ranging between 5 and 50 μg/ml mimicking human serum levels, has a significant effect on reducing tumor cell proliferation of A549 cells, mainly by altering cell cycle progression. Importantly, we provide evidence that adiponectin clearly inhibits in a dose- and time-dependent manner CREB phosphorylation (activation) and, at least in part, also the level of CREB protein itself, preceding and accompanying the anti-proliferative effects in response to adiponectin. Moreover, in agreement with previous studies demonstrating that CREB over-expression occurs in many tumors, we also show by western-blotting from lung specimen that CREB is significantly up-regulated in NSCLC samples compared to adjacent normal tissues from six patients. CONCLUSIONS: Overall, our results represent the first evidence of CREB inhibition by adiponectin and may provide new insight into therapeutic strategies for lung cancer.
Authors: E Nigro; P Schettino; R Polito; O Scudiero; M L Monaco; G D De Palma; A Daniele Journal: Mol Cell Biochem Date: 2018-02-14 Impact factor: 3.396
Authors: Ersilia Nigro; Fabio Perrotta; Maria Ludovica Monaco; Rita Polito; Pia Clara Pafundi; Maria Gabriella Matera; Aurora Daniele; Andrea Bianco Journal: Biomolecules Date: 2020-06-18