The antihistamine deptropine induces hepatoma cell death through blocking autophagosome-lysosome fusion

Yu Chih Liang, Chi Ching Chang, Ming Thau Sheu, Shyr Yi Lin, Chia Chen Chung, Chang Ting Teng, Fat Moon Suk

研究成果: 雜誌貢獻文章同行評審

14 引文 斯高帕斯(Scopus)


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

頁(從 - 到)1-14
出版狀態已發佈 - 6月 2020

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究


深入研究「The antihistamine deptropine induces hepatoma cell death through blocking autophagosome-lysosome fusion」主題。共同形成了獨特的指紋。