title: Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells.
abstract: Surgery is the primary therapy for pheochromocytoma (PHEO), a catecholamine-producing tumor. Benign and malignant PHEO could develop recurrences, and the intraoperative risk of recurrent PHEO is an important unresolved issue. Non-surgical treatments of PHEO recurrence would therefore better prepare patients for reintervention as well as provide them with palliative management. We investigated the effects of the new somatostatin analog (pasireotide) SOM230 versus octreotide (OCT) in primary PHEO cell cultures (Pheo-c). Pheo-c from six benign surgical samples were set up and characterized by immunocytochemistry. Real-time PCR, using both PHEO tissues and Pheo-c, showed different levels of somatostatin receptor(1-5) mRNA expression. Cells treated with various doses of OCT or SOM230 for 48 and 72 h were analyzed to assess their effects on cell proliferation and apoptosis and catecholamine levels. Even if reduction of cell viability was observed in Pheo-c treated for 48 h with either OCT or SOM230 and this effect increased after 72 h, a more significant inhibition of cell growth as well as a significantly higher induction of apoptosis was seen in Pheo-c treated with SOM230 versus OCT. In particular, apoptosis in Pheo-c was detected after 48 h and was associated with increased expression and activation of caspase-3 and cleaved poly(ADP-ribose) polymerase. OCT 10(-6) M and SOM230 10(-7) M significantly reduced catecholamine levels. Our results indicate that while both OCT and SOM230 modulate cell growth and apoptosis and catecholamine levels in Pheo-c through specific receptors, SOM230 is more effective. This improves our knowledge on the mechanism of SOM230 action in PHEO and supports a possible therapeutic use in benign PHEO recurrence.
authors.affiliation: Endocrine Unit, Department of Clinical and Experimental Medicine and Surgery and Endo-Surgery Unit, Second University of Naples, 80131 Naples. daniela.pasquali@unina2.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Pasquali
authors.forename: Valentina
authors.initials: V
authors.lastname: Rossi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Conzo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pannone
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Bufo
authors.forename: Annamaria
authors.initials: A
authors.lastname: De Bellis
authors.forename: Andrea
authors.initials: A
authors.lastname: Renzullo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bellastella
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Vallone
authors.forename: Antonio
authors.initials: A
authors.lastname: Bellastella
authors.forename: Antonio A
authors.initials: AA
authors.lastname: Sinisi
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology; D010673:Pheochromocytoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D002395:Catecholamines; D017481:Receptors, Somatostatin; D013004:Somatostatin; C517782:pasireotide; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D015282:Octreotide