Taiwanin A targets non-steroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma.

Abstract

Taiwanin A (α,β-bis(piperonylidene)-γ-butyrolactone) is extracted from Taiwania cryptomerioides. Taiwanin A is extracted from tree bark and exhibits antitumor activity in breast, liver, and lung cancer cell lines. The objective of this study was to demonstrate the cytotoxicity of Taiwanin A against tumor cells by increasing the expression of non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1). NAG-1 has been reported to exhibit antitumor and proapoptotic activities, suggesting potential use in cancer therapy. Inhibiting NAG-1 mRNA expression in A549 reduced the cytotoxicity caused by Taiwanin A. Furthermore, the c-Jun-N-terminal kinase/Ste20-related protein proline/alanine-rich kinase (JNK/SPAK) pathway played a key role in the influence of NAG-1 on cell viability, whereas the addition of the JNK pathway inhibitor SP600125 resulted in an inhibitory effect on NAG-1 and recovery of Taiwanin-A-treated cells. A xenograft tumor model demonstrated that Taiwanin A dose-dependently significantly decreases tumor-mediated growth in nude mice by increasing the NAG-1 expression accompanying tumor apoptosis. These data supported the hypothesis that Taiwanin A inhibits lung carcinoma growth by increasing NAG-1 expression through the JNK pathway both in vivo and in vitro. This result can contribute to a compound design for increasing cytotoxicity activity in the future.

• Authors: Horng-Jyh Harn, Hong-Meng Chuang, Li-Fu Chang, Angela Yu Hsuan Huang, Shin-Ta Hsieh, Shinn-Zong Lin, Chih-Wei Chou, Yueh-Hsiung Kuo, Tzyy-Wen Chiou
• Journal: Fitoterapia (Fitoterapia) Vol. 99 Pg. 227-35 (Dec 2014) ISSN: 1873-6971 [Electronic] Netherlands
• PMID: 25173462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Anthracenes
• Antineoplastic Agents, Phytogenic
• Furans
• GDF15 protein, human
• Growth Differentiation Factor 15
• Lignans
• taiwanin A
• pyrazolanthrone
• Protein Serine-Threonine Kinases
• STK39 protein, human
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Anthracenes (pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis
• Cell Line, Tumor
• Furans (pharmacology)
• Growth Differentiation Factor 15 (metabolism)
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Lignans (pharmacology)
• Lung Neoplasms (metabolism)
• MAP Kinase Signaling System (drug effects)
• Mice, Inbred BALB C
• Mice, Nude
• Protein Serine-Threonine Kinases (metabolism)
• Xenograft Model Antitumor Assays