Thiazolidinediones inhibit the growth of PC12 cells both in vitro and in vivo.
Thiazolidinediones (TZDs) have recently been proposed as a therapy for PPARgamma-expressing tumors. Pheochromocytoma (PHEO) is associated with high morbidity and mortality due to excess catecholamine production, and few effective drug therapies currently exist. We investigated the effects of TZDs on PHEO both in vitro and in vivo. PPARgamma protein was expressed in human adrenal PHEO tissues as well as in rat PHEO cells, PC12. TZDs, including rosiglitazone (RGZ) and pioglitazone (PGZ), inhibited proliferation of PC12 cells in a dose-dependent manner and increased casapse-3 expression of PC12 cells. TZDs also reduced expression of cyclin E and cyclin-dependent kinase2. RGZ inhibited nerve growth factor-induced neurite outgrowth and reduced expression of catecholamine-synthesizing enzymes. Finally, rat PHEO growth generated by subcutaneous injection of PC12 cells was slowed in an RGZ-treated mouse. These data suggest that TZDs may be a promising therapeutic approach for medical treatment for PHEO.
Kim
Sang Wan
SW
Department of Internal Medicine, Seoul National University, College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul 110-774, Republic of Korea.
Choi
Ok Kyung
OK
Chang
Mee Soo
MS
Shin
Chan Soo
CS
Park
Kyong Soo
KS
Kim
Seong Yeon
SY
D000310:Adrenal Gland Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019927:Cyclin E / Q000037:antagonists & inhibitors; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism* / Q000517:prevention & control; D000077205:Pioglitazone; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019927:Cyclin E; D019394:Ki-67 Antigen; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D020932:Nerve Growth Factor; D051357:Cyclin-Dependent Kinase 2; D053148:Caspase 3; D000077205:Pioglitazone