Anti-tumor activity of three ginsenoside derivatives in lung cancer is associated with Wnt/β-catenin signaling inhibition.

Abstract

Numerous compounds isolated from Ginseng have been shown to exhibit various biological activities, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activities. Recent research has focused on the potential values of these compounds in the prevention and treatment of human cancers. The anti-tumor activity of 25-hydroxyprotopanaxadiol (25-OH-PPD), a natural compound isolated from Panax ginseng, has been established in previous study. In the current study, we investigated the anti-tumor activity of three derivatives of 25-OH-PPD, namely xl, 1c, and 8b with respect to lung cancer. All three compounds significantly inhibited the growth of the human lung cancer cells A549 and H460. Oral administration of these compounds significantly inhibited the growth of xenograft tumors in mice without affecting body weight. Further mechanistic study demonstrated that these compounds could decrease the expression levels of β-catenin and its downstream targets Cyclin D1, CDK4, and c-myc in lung cancer cells. Taken together, the results suggested that the anti-growth activity exerted by these 25-OH-PPD derivatives against lung cancer cells probably involved β-catenin-mediated signaling pathway, a finding that could have important implication for chemotherapeutic strategy aiming at the treatment of lung cancer.

• Authors: Xiuli Bi, Xichun Xia, Teng Mou, Bowen Jiang, Dongdong Fan, Peng Wang, Yafei Liu, Yue Hou, Yuqing Zhao
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 742 Pg. 145-52 (Nov 05 2014) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25199964 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• 12-O-(chloracetyl)dammarane-3,20,25-triol
• 25-hydroxyprotopanaxadiol
• 3-O-(Boc-arginyl)dammarane-12,20,25-triol
• 3-O-(alanyl)dammarane-12,20,25-triol
• Antineoplastic Agents, Phytogenic
• CTNNB1 protein, human
• Ginsenosides
• beta Catenin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Ginsenosides (chemistry, pharmacology)
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Male
• Mice
• Mice, Nude
• Neoplasm Invasiveness
• Panax
• Wnt Signaling Pathway (drug effects)
• Xenograft Model Antitumor Assays
• beta Catenin (metabolism)