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

• Published in: European journal of pharmacology Vol. 742; pp. 145 - 152
• Main Authors: Bi, Xiuli, Xia, Xichun, Mou, Teng, Jiang, Bowen, Fan, Dongdong, Wang, Peng, Liu, Yafei, Hou, Yue, Zhao, Yuqing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.11.2014
• Subjects: Animals; Anti-tumor activity; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; beta Catenin - metabolism; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapeutic; Derivatives of 25-OH-PPD; G1 Phase Cell Cycle Checkpoints - drug effects; Ginsenosides - chemistry; Ginsenosides - pharmacology; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Mice; Mice, Nude; Neoplasm Invasiveness; Panax; Wnt Signaling Pathway - drug effects; Xenograft Model Antitumor Assays; β-catenin; β-catenin; Derivatives of 25-OH-PPD; Chemotherapeutic; Lung cancer; Anti-tumor activity; Cell cycle
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2014.08.032

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. [Display omitted]