In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells

Yi Lin Chen, Shinn Zong Lin, Jang Yang Chang, Yeung Leung Cheng, Nu Man Tsai, Shee Ping Chen, Wen Liang Chang, Horng Jyh Harn

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73 Citations (Scopus)

Abstract

We previously demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (BS-AE) 60 μg/ml has anti-proliferation activity and apoptotic effects on A549 non-small cell lung cancer (NSCLC). A novel lignan, isochaihulactone (4-benzo[1,3]dioxol-5-ylmethyl-3(3,4,5-trimethoxyl-benzylidene)-dihydro-furan-2-one), was isolated from BS-AE and identified from spectral evidence (1H NMR, 13C NMR, IR, and MS) and by comparison with authentic synthetic standards. Isochaihulactone was cytotoxic (IC50 = 10-50 μM) in a variety of human tumor cell lines. In in vitro and in vivo microtubule assembly assays, it inhibited tubulin polymerization in a concentration-dependent manner. As determined by flow cytometry, isochaihulactone caused G2/M phase arrest and apoptosis in a time- and concentration-dependent manner. G2/M arrest was correlated with increased p21/WAF1 levels, downregulation of the checkpoint proteins cyclin B1/cdc2 and mobility shift of cdc25C. Moreover, isochaihulactone (30 and 50 mg/kg) inhibited the growth of non-small cell lung carcinoma A549 xenograft in nude mice. These findings indicate isochaihulactone is a promising new antimitotic anticancer compound with potential for clinical application in the future.

Original languageEnglish
Pages (from-to)308-319
Number of pages12
JournalBiochemical Pharmacology
Volume72
Issue number3
DOIs
Publication statusPublished - 2006 Jul 28

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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