Heat Shock Protein 90 Inhibitors AUY922, BIIB021 and SNX5422 Induce Bim-mediated Death of Thyroid Carcinoma Cells

• Published in: Anticancer research Vol. 40; no. 11; pp. 6137 - 6150
• Main Authors: KIM, SI HYOUNG, CHO, YUN KYUNG, HUH, JI HYE, KANG, JUN GOO, IHM, SUNG-HEE, CHOI, MOON GI, LEE, SEONG JIN
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.11.2020
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; AKT protein; Antibodies; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; Bcl-2-Like Protein 11 - metabolism; Benzamides - pharmacology; BIM protein; Cancer; Cancer therapies; Caspase-3; Cell death; Cell Line, Tumor; Cell survival; Cell Survival - drug effects; Cell viability; Cholecystokinin; Cytotoxicity; Drug dosages; Experiments; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Flow cytometry; Heat; Heat shock proteins; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humans; Indazoles - pharmacology; Inhibitors; Isoxazoles - pharmacology; Kinases; Medical prognosis; Metastasis; Penicillin; Proto-Oncogene Proteins c-akt - metabolism; Pyridines - pharmacology; Resorcinols - pharmacology; Signal Transduction - drug effects; Software; Survival; Thyroid; Thyroid cancer; Thyroid carcinoma; Thyroid Neoplasms - enzymology; Thyroid Neoplasms - pathology; Toxicity; United States > US; South Korea; SNX5422; HSP90 inhibitor; AUY922; Bim; BIIB021; Thyroid carcinoma
• ISSN: 0250-7005; 1791-7530; 1791-7530
• DOI: 10.21873/anticanres.14634

Heat shock protein 90 (HSP90) controls maturation of oncogenic client proteins of cancer cells, and thus we studied the effect of HSP 90 inhibitors on cell survival and survival-related mediators in thyroid carcinoma cells. Human TPC-1 and SW1736 thyroid carcinoma cells were utilized. Cell viability, cytotoxic activity and apoptosis were estimated using CCK-8 assay, cytotoxicity assay and FACS analysis, respectively. AUY922, BIIB021 and SNX5422 decreased cell viability, and increased cytotoxic activity and the proportion of apoptotic cells. The protein levels of cleaved PARP, cleaved caspase-3, Bax and Bim were elevated, and Bcl2 protein levels were reduced. Knockdown of Bax did not change cell viability, cytotoxic activity, the proportion of apoptotic cells and cleaved caspase-3 protein levels. Meanwhile, knockdown of Bim enhanced cell viability, and diminished cytotoxic activity, the proportion of apoptotic cells and cleaved caspase-3 protein levels. AUY922, BIIB021 and SNX5422 increased the protein levels of phospho-AMPK, and decreased those of phospho-ERK1/2, and total and phospho-AKT. AUY922, BIIB021 and SNX5422 induce cytotoxicity by modulating Bim and ERK1/2, AKT and AMPK signaling in thyroid carcinoma cells.