Inhibition of glycolysis and stimulation of mitochondrial biogenesis lead to increased ROS levels and cell death in HNF-1ß positive clear cell carcinoma.

ABSTRACT: Ovarian clear cell carcinoma is characterized by HNF-1ß overexpression and is known to be resistant to chemotherapy. An inhibitor screening that specifically targets HNF-1ß led us to identify Actinonin as a candidate for cancer treatment. Actinonin, which is known to inhibit aminopeptidase M, has also been recognized for its antibacterial properties. We confirmed that GSK-3ß interference/inhibition, as a component of the HNF-1ß pathway, combined with Actinonin, has a highly potent antitumor effect compared to monotherapy. The same effect was observed in renal clear cell carcinoma lines expressing HNF-1ß. Actinonin promoted mitochondrial production by suppressing aerobic respiration, which decreased AMPK levels and increased ROS production. However, it also elevated GADD45α expression and i

SUBMITTER: Kawahara N 

PROVIDER: S-EPMC12669797 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature