title: Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism.
abstract: Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm3and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution1H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Furtherin vivopreclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action.
authors.affiliation: JHU ICMIC Program, Russell H. Morgan, Division of Cancer Imaging Research, Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Penet
authors.affiliation: JHU ICMIC Program, Russell H. Morgan, Division of Cancer Imaging Research, Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine , Baltimore, MD , USA.
authors.forename: Balaji
authors.initials: B
authors.lastname: Krishnamachary
authors.affiliation: JHU ICMIC Program, Russell H. Morgan, Division of Cancer Imaging Research, Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine , Baltimore, MD , USA.
authors.forename: Flonne
authors.initials: F
authors.lastname: Wildes
authors.affiliation: JHU ICMIC Program, Russell H. Morgan, Division of Cancer Imaging Research, Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine , Baltimore, MD , USA.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Mironchik
authors.affiliation: Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Mezzanzanica
authors.affiliation: Section of Molecular and Cellular Imaging, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Podo
authors.affiliation: Neurobiology of Cellular Interactions and Neurophysiopathology (NICN), Aix Marseille Univ, CNRS , Marseille , France.
authors.forename: Max
authors.initials: M
authors.lastname: de Reggi
authors.affiliation: Neurobiology of Cellular Interactions and Neurophysiopathology (NICN), Aix Marseille Univ, CNRS , Marseille , France.
authors.forename: Bouchra
authors.initials: B
authors.lastname: Gharib
authors.affiliation: JHU ICMIC Program, Russell H. Morgan, Division of Cancer Imaging Research, Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Zaver M
authors.initials: ZM
authors.lastname: Bhujwalla
keywords: ascites; choline metabolism; high-resolution MRS; metastasis; orthotopic model; ovarian cancer; pantethine