title: Structural modification of ginsenoside Rh(2) by fatty acid esterification and its detoxification property in antitumor.
abstract: Ginsenoside Rh(2), one of the most important ginsenosides with anticancer properties in red ginseng, has been developed as principal antitumor ingredient for clinical use. However, the cytotoxicity test in human hepatocyte cell line QSG-7701 (IC(50) 37.3μM) indicated that Rh(2) might show strong cytotoxic side-effect on the normal liver cells. For blunting the toxicity, Rh(2) was structurally modified by reacting with octanoyl chloride to give a dioctanoyl ester of Rh(2) (D-Rh(2)) in the present study. MTT assay in QSG-7701 cell line in vitro showed that the cytotoxicity of D-Rh(2) on human hepatocyte cells (IC(50) 80.5μM) was significantly lower than that of Rh(2). While antitumor xenograft assay in mice bearing H22 liver cancer cells in vivo showed that the antitumor activity of D-Rh(2) retained to be strong as that of Rh(2). According to previous pharmacokinetic studies, the fatty acid esterification of Rh(2) might be of detoxification reaction to cells. Additionally, D-Rh(2) showed significant enhancement on increasing thymus index at the dose of 10mg/kg compared with vehicle treated control group. Thus, D-Rh(2) might indirectly affect tumor growth by stimulating lymphocytes to become cytotoxic to tumor cells. Finally, our findings suggested that D-Rh(2), the fatty acid ester of Rh(2), might attenuate the side-effect by detoxification to human normal cell and could be a more potential candidate for developing as an antitumor drug.
authors.affiliation: College of Chinese Medicinal Material, Jilin Agricultural University, Changchun, Jilin 130118, China.
authors.forename: Gong-Qing
authors.initials: GQ
authors.lastname: Wei
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Wen-Cong
authors.initials: WC
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.forename: Wei-Yun
authors.initials: WY
authors.lastname: Zhang
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Chen
authors.forename: Jin-Zhang
authors.initials: JZ
authors.lastname: Zeng
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Zhang
authors.forename: Quan-Cheng
authors.initials: QC
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005227:Fatty Acids / Q000737:chemistry*; D036145:Ginsenosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008968:Molecular Conformation; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D013154:Spleen / Q000187:drug effects; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D005227:Fatty Acids; D036145:Ginsenosides; C055305:ginsenoside Rh2