title: Caspase-mediated pro-apoptotic interaction of panaxadiol and irinotecan in human colorectal cancer cells.
abstract: OBJECTIVE
  Panaxadiol is a purified sapogenin of ginseng saponins that exhibits anticancer activity. Irinotecan is a second-line anticancer drug, but clinical treatment with irinotecan is limited due to its side effects. In this study, we have investigated the possible synergistic anticancer effects of panaxadiol and irinotecan on human colorectal cancer cells and explored the potential role of apoptosis in their synergistic activity.
  
  
  RESULTS
  The combination of panaxadiol and irinotecan significantly enhanced antiproliferative effects in HCT-116 cells (P< 0.05). Cell cycle analysis demonstrated that combining irinotecan treatment with panaxadiol significantly increased the G1-phase fractions of cells, compared with irinotecan treatment alone. In apoptotic assays, the combination of panaxadiol and irinotecan significantly increased the percentage of apoptotic cells compared with irinotecan alone (P<0.01). Increased activity of caspase-3 and caspase-9 was observed after treating with panaxadiol and irinotecan. The synergistic apoptotic effects were supported by docking analysis, which demonstrated that panaxadiol and irinotecan bound two different chains of the caspase-3 protein.
  
  
  CONCLUSIONS
  Data from this study suggested that caspase-3- and caspase-9-mediated apoptosis may play an important role in the panaxadiol enhanced antiproliferative effects of irinotecan on human colorectal cancer cells.
authors.affiliation: Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Guang-Jian
authors.initials: GJ
authors.lastname: Du
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Somogyi
authors.forename: Tyler
authors.initials: T
authors.lastname: Calway
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D045325:HCT116 Cells; D006801:Humans; D000077146:Irinotecan; D005894:Panax / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D036145:Ginsenosides; D010936:Plant Extracts; C004564:panaxadiol; D000077146:Irinotecan; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D002166:Camptothecin