title: Induction of differentiation by panaxydol in human hepatocarcinoma SMMC-7721 cells via cAMP and MAP kinase dependent mechanism.
abstract: Panaxydol (PND) is one of the main non-peptidyl small molecules isolated from the lipophilic fractions of Panax notoginseng. The present study was carried out to demonstrate the potential effects of panaxydol on the induction of differentiation of human liver carcinoma cell lines SMMC-7721. Cell viability was evaluated by MTT method and Trypan blue exclusion assay respectively. The changes of morphology were detected by transmission electron microscope. Inhibitors were applied to detect the signaling pathway of differentiation. The level of intracellular cyclic AMP was determined by radioimmunoassay. The expression of p-ERK, Id1, and p21 were determined by Western blot. We found that panaxydol inhibit the proliferation of SMMC-7721 cells and caused the morphology and ultrastructure changes of SMMC-7721. Moreover, panaxydol dose-dependently increased the secretion of albumin and alkaline phosphatase activity, and decreased the secretion of AFP correspondingly. These changes of differentiation markers in SMMC-7721 can be reversed by the protein kinase A inhibitor RpcAMPS and by MAP kinase kinase 1/2 inhibitor U0126 or sorafenib. Intracellular cAMP was elevated by panaxydol in SMMC-7721 cells. Panaxydol dose-dependently decreased the expression of regulatory factors Id1 and increased the protein levels of p21 and p-ERK1/2 correspondingly. It suggested panaxydol might be of value for further exploration as a potential anti-cancer agent via cAMP and MAP kinase-dependent mechanism.
authors.affiliation: School of Pharmacy, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Ze-Jian
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Lin-Chen
authors.initials: LC
authors.lastname: Guo
authors.forename: Min
authors.initials: M
authors.lastname: Yin
authors.forename: Yong Ning
authors.initials: YN
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D003864:Depression, Chemical; D053280:Diynes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000032:analysis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism* / Q000502:physiology; D005233:Fatty Alcohols / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D053280:Diynes; D004365:Drugs, Chinese Herbal; D005233:Fatty Alcohols; C519374:Panax notoginseng extract; C055778:panaxydol; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases