Resorcylic acid lactone L-783,277 inhibits the growth of the human adrenal cancer cell line H295R in vitro.
The resorcylic acid lactone L-783,277, isolated from a Phoma sp. (ATCC 74403), is a potent and specific inhibitor of MEK (Map kinase kinase) that exerts very interesting pharmacological activities including anti-neoplastic properties. However, the role of this compound in the regulation of endocrine-related cancer cell growth and tumor progression remains unknown. In the present study we have evaluated the effect of L-783,277 on the viability, proliferation and cell cycle of the human adrenocortical carcinoma cell line H295R. L-783,277 inhibited viability (IC50 of 22 microM) and cell proliferation (IC50 of 21 microM) of H295R. At concentrations of 10(-6)-10(-8)M this effect was associated with the accumulation of H295R cells in S-phase, whereas at concentrations of 10(-9)-10(-10)M a prolonged G1-phase and reduced transition into S-phase were observed. Our findings demonstrate for the first time the anti-proliferative action of L-783,277 on the human adrenocortical H295R cell line.
Lawnicka
H
H
Department of Immunoendocrinology, First Chair of Endocrinology, Medical University of Lodz, Lodz, Poland.
Kowalewicz-Kulbat
M
M
Sicinska
P
P
Altmann
K H
KH
Hofmann
T
T
Stepien
H
H
D000306:Adrenal Cortex Neoplasms / Q000201:enzymology / Q000473:pathology*; D018268:Adrenocortical Carcinoma / Q000201:enzymology / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012118:Resorcinols / Q000494:pharmacology*
D000970:Antineoplastic Agents; C405053:L 783277; D007783:Lactones; D047428:Protein Kinase Inhibitors; D012118:Resorcinols; D020929:Mitogen-Activated Protein Kinase Kinases