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

Abstract

We previously demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (BS-AE) 60 microg/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 ((1)H NMR, (13)C NMR, IR, and MS) and by comparison with authentic synthetic standards. Isochaihulactone was cytotoxic (IC(50)=10-50 microM) 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.

• Authors: Yi-Lin Chen, Shinn-Zong Lin, Jang-Yang Chang, Yeung-Leung Cheng, Nu-Man Tsai, Shee-Ping Chen, Wen-Liang Chang, Horng-Jyh Harn
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 72 Issue 3 Pg. 308-19 (Jul 28 2006) ISSN: 0006-2952 [Print] England
• PMID: 16782069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzodioxoles
• Lignans
• Plant Extracts
• Tubulin
• isochaihulactone
• 4-Butyrolactone

Topics

• 4-Butyrolactone (analogs & derivatives, chemistry, pharmacology)
• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis (drug effects)
• Benzodioxoles (chemistry, pharmacology)
• Bupleurum (chemistry)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Shape (drug effects)
• Dose-Response Relationship, Drug
• G2 Phase (drug effects)
• Humans
• Inhibitory Concentration 50
• Lignans (chemistry, pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Fluorescence
• Microtubules (drug effects, metabolism)
• Phosphorylation (drug effects)
• Plant Extracts (chemistry, pharmacology)
• Plant Roots (chemistry)
• Tubulin (metabolism)
• Weight Gain (drug effects)
• Xenograft Model Antitumor Assays (methods)