title: U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving Phosphoinositide-specific Phospholipases C.
abstract: The definition of the number and nature of the signal transduction pathways involved in the pathogenesis and the identification of the molecules promoting metastasis spread might improve the knowledge of the natural history of osteosarcoma, also allowing refine the prognosis and opening the way to novel therapeutic strategies. Phosphatydil inositol (4,5) bisphosphate (PIP2), belonging to the Phosphoinositide (PI) signal transduction pathway, was related to the regulation of ezrin, an ezrin-radixin-moesin protein involved in metastatic osteosarcoma spread. The levels of PIP2 are regulated by means of the PI-specific Phospholipase C (PLC) enzymes. Recent literature data suggested that in osteosarcoma the panel of expression of PLC isoforms varies in a complex and unclear manner and is related to ezrin, probably networking with Ras GTPases, such as RhoA and Rac1. We analyzed the expression and the subcellular localization of PLC enzymes in cultured human osteosarcoma MG-63 cells, commonly used as an experimental model for human osteoblasts, using U-73122 PLC inhibitor, U-73343 inactive analogue, and by silencing ezrin. The treatment with U-73122 significantly reduces the number of MG-63 viable cells and contemporarily modifies the expression and the subcellular localization of selected PLC isoforms. U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving PI-specific Phospholipases C.
authors.affiliation: Sensory Organs Department, Policlinico Umberto I, Faculty of Medicine and Dentistry, Sapienza University of Rome, viale dell'Università, 33, 00157 Rome, Italy.
authors.forename: Vincenza Rita
authors.identifier: 0000-0001-7584-6199
authors.initials: VR
authors.lastname: Lo Vasco
authors.affiliation: Medico-Surgical Sciences and Biotechnology Department, Polo Pontino- Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Leopizzi
authors.affiliation: Medico-Surgical Sciences and Biotechnology Department, Polo Pontino- Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Di Maio
authors.affiliation: Medico-Surgical Sciences and Biotechnology Department, Polo Pontino- Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Della Rocca
keywords: DMSO; MG-63; Oncology; Osteosarcoma; Phosphoinositide; Phospholipase C; U-73122; U-73343