The Antihistamine Deptropine Induces Hepatoma Cell Death through Blocking Autophagosome-Lysosome Fusion

摘要: Some antihistamines have exhibited significant antitumor activity alone or in combination with other therapies vitro and clinical studies. However, the underlying mechanisms of how inhibit hepatocellular carcinoma proliferation are still unknown. We first screened antiproliferation 12 benzocycloheptene structural-analogue drugs, results showed that deptropine was most potent inhibitor both Hep3B HepG2 human hepatoma cells. Deptropine significantly increased light chain 3B-II (LC3B-II) expression but did not induce sequestosome 1 (SQSTM1/p62) degradation either cell line. Interestingly, autophagy-related proteins, such as 7 (ATG7), vacuolar protein sorting 34 (VPS34), phosphorylated adenosine 5'-monophosphate-activated kinase (AMPK), B (PKB, also known Akt), no change deptropine-treated inhibited processing cathepsin L from its precursor form to mature form. Immunofluorescence microscopy an increase autophagosomes cells, blocked fusion between lysosomes. In a xenograft nude mice model, 2.5 mg/kg great inhibitory effect on tumor growth. These suggest can vivo death, might be mediated through inhibiting autophagy by blocking autophagosome-lysosome fusion.