BDH2 promotes apoptosis and autophagy of lung adenocarcinoma cells via Akt/mTOR pathway

• Published in: General physiology and biophysics Vol. 41; no. 2; p. 115
• Main Authors: Nie, Yongli, Mei, Xiong, Cao, Fengjun, Zhu, Xueni
• Format: Journal Article
• Language: English
• Published: Slovakia 01.03.2022
• Subjects: Adenocarcinoma of Lung; Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; Humans; Hydroxybutyrate Dehydrogenase - metabolism; Lung Neoplasms - metabolism; Proto-Oncogene Proteins c-akt - metabolism; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0231-5882
• DOI: 10.4149/gpb_2022002

Cytoprotective autophagy induces tumor cell apoptosis or autophagic programmed cell death. Autophagy and apoptosis are implicated in the pathogenesis of lung cancer, especially lung adenocarcinoma. 3-Hydroxybutyrate dehydrogenase type 2 (BDH2), a rate-limiting catalyzer in the regulation of intracellular iron metabolism and siderophore biogenesis, has been shown to be a tumor suppressor through promotion of cell apoptosis and autophagy. However, the biological role of BDH2 on lung adenocarcinoma cell apoptosis and autophagy remains unclear. Data from Western blot and qRT-PCR showed that BDH2 was down-regulated in lung adenocarcinoma cells (A549, NCI-H1975, PC9) compared to normal human lung cells (BEAS-2B). Functional assays demonstrated that pcDNA-mediated over-expression of BDH2 reduced cell viability of lung adenocarcinoma cells, and repressed the proliferation. Cell apoptosis of lung adenocarcinoma was promoted by BDH2 over-expression with up-regulation of Bax and cleaved caspase-3. Over-expression of BDH2 reduced protein expression of p62 in lung adenocarcinoma cells, enhanced LC3 and Beclin-1. Phosphorylation of AKT and mTOR in lung adenocarcinoma cells were reduced by BDH2 over-expression. In conclusion, BDH2 functioned as a tumor suppressor in lung adenocarcinoma through promotion of Akt/mTOR-mediated cell apoptosis and autophagy.