title: TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol.
abstract: Among important components of American ginseng, protopanaxadiol (PPD) showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound.
authors.affiliation: Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Zejuan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
authors.affiliation: Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Calway
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA; Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL 60637, USA. Electronic address: cyuan@dacc.uchicago.edu.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D005894:Panax / Q000737:chemistry; D012502:Sapogenins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects* / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012502:Sapogenins; D053221:TNF-Related Apoptosis-Inducing Ligand; C062916:protopanaxadiol
keywords: Apoptosis; Gene expression; Human colorectal cancer; Microarray; Panax quinquefolius; Protopanaxadiol; Tumor necrosis factor; Xenograft