Synthesis of novel diosgenyl saponin analogues and apoptosis-inducing activity on A549 human lung adenocarcinoma

Bo Wang, Jaemoo Chun, Yang Liu, Lina Han, Yan Shi Wang, Eun Ji Joo, Yeong Shik Kim, Mao Sheng Cheng

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We synthesized a diosgenyl saponin bearing a unique disaccharide from the natural product β-hederin, together with twelve glycosylated derivatives and determined their cytotoxicity against five different human cancer cell lines. Most of them showed weak cytotoxicity, with the exception of compound 20, diosgenyl α-l-rhamnopyranosyl-(1→2)-[α-l-arabinopyranosyl- (1→4)]-α-l-arabinopyranoside, which exhibited strong cytotoxicity against A549 cells. The cytotoxicity of 20 was associated with apoptotic cell death, which was characterized by morphological changes, chromatin condensation, DNA fragmentation, and phosphatidylserine externalization. Compound 20 induced apoptosis of A549 cells through a caspase-8-mediated extrinsic pathway and a caspase-9-mediated intrinsic pathway. In addition, phosphorylation of JNK increased but the phosphorylation of ERK decreased after treatment with 20. These results provide a basic mechanism for the anticancer activity of 20.

Original languageEnglish (US)
Pages (from-to)8822-8834
Number of pages13
JournalOrganic and Biomolecular Chemistry
Volume10
Issue number44
DOIs
StatePublished - Nov 28 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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