Troglitazone-Induced Autophagic Cytotoxicity in Lung Adenocarcinoma Cell Lines.
Biol Pharm Bull
; 45(3): 276-283, 2022.
Article
en En
| MEDLINE
| ID: mdl-35228393
ABSTRACT
Lung cancer is the leading cause of cancer-related deaths worldwide. Troglitazone (TGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, is a potential antitumor agent. However, the action mechanism of TGZ in lung adenocarcinoma cells has not been completely elucidated. To assess this mechanism and the anticancer effects of TGZ in human lung adenocarcinoma cell lines (A549 and H1975), we investigated the involvement of PPARγ, apoptosis, the mitogen-activated protein kinase (MAPK) pathway, protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, and autophagy. Cell viability was measured using fluorescence-based assays. Apoptotic cells were detected by Hoechst 33342 and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining; protein expression was detected by Western blotting. TGZ inhibited cell proliferation in a dose-dependent manner in both cell lines, and the effect was not suppressed by a PPARγ inhibitor. Additionally, TGZ increased apoptotic cell number and upregulated p38 and c-Jun N-terminal kinase (JNK) phosphorylation; however, p38 and JNK inhibitors did not block TGZ-mediated inhibition of cell proliferation in either cell line. TGZ also upregulated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, whereas an ERK1/2 inhibitor enhanced TGZ-mediated cytotoxicity in A549 cells. Additionally, TGZ increased LC3-II expression, and chloroquine (an autophagy inhibitor) attenuated TGZ-mediated inhibition of cell proliferation. These findings suggest that TGZ-induced inhibition of cell proliferation is PPARγ independent. TGZ-mediated inhibition of cell proliferation was accompanied by apoptosis and independent of the MAPK signaling pathway. These results suggest that TGZ inhibits cell proliferation through autophagy-induced cytotoxicity. This study demonstrated that chemotherapy using TGZ may be effective for lung adenocarcinoma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiazolidinedionas
/
Adenocarcinoma del Pulmón
Límite:
Humans
Idioma:
En
Revista:
Biol Pharm Bull
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
2022
Tipo del documento:
Article