Anti-tumor activity of three novel derivatives of ginsenoside on colorectal cancer cells

• Published in: Steroids Vol. 80; pp. 24 - 29
• Main Authors: Xia, Xichun, Jiang, Bowen, Liu, Wei, Wang, Peng, Mou, Yanhua, Liu, Yafei, Zhao, Yuqing, Bi, Xiuli
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2014
• Subjects: Anti-tumor activity; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapeutic; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Derivatives of 25-OH-PPD; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Ginsenosides - chemistry; Ginsenosides - isolation & purification; Ginsenosides - pharmacology; HCT116 Cells; HT29 Cells; Humans; Molecular Conformation; Panax - chemistry; Stereoisomerism; Structure-Activity Relationship; Tumor Cells, Cultured; Derivatives of 25-OH-PPD; Chemotherapeutic; Anti-tumor activity; Apoptosis
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2013.11.018

[Display omitted] •Three derivatives of 25-hydroxyprotopanaxadiol are specific to inhibite the growth of human colorectal cancer cells.•They have lesser effect on the growth of normal primary muscle cells and spleno-lymphocytes compared with cancer cells.•They could induce apoptosis via activating the components of caspase-signaling pathways in HCT116 cells. 25-Hydroxyprotopanaxadiol (25-OH-PPD) is a natural compound isolated from Panax ginseng, and its anti-tumor activity has been studied in previous publication. In the current study, we investigated the anti-tumor activity of three novel derivatives synthesized from 25-OH-PPD, namely (20R)-12β-O-(l-chloracetyl)-dammarane-3β, 20, 25-triol (xl), (20R)-3β-O-(l-alanyl)-dammarane-12β, 20, 25-triol (1c), and (20R)-3β-O-(Boc-l-arginyl)-dammarane-12β, 20, 25-triol (8b). All three compounds significantly inhibited the growths of human colorectal cancer cells, while having lesser effect on the growth of normal primary muscle cells and spleno-lymphocytes. Further mechanistic study demonstrated that these compounds could induce apoptosis by activating the components of caspase-signaling pathways in HCT116 cells, but not in spleno-lymphocytes. Taken together, the results suggested that 25-OH-PPD derivatives exerted promising anti-tumor activity that is specific to human colorectal cancer cells, and may therefore represent a potential chemotherapeutic strategy for the treatment of colorectal cancer.