Novel ginsenosides 25-OH-PPD and 25-OCH3-PPD as experimental therapy for pancreatic cancer: anticancer activity and mechanisms of action.
We recently isolated and characterized two novel ginsenosides, 25-OH-PPD and 25-OCH(3)-PPD. We investigated whether these ginsenosides could represent safe and effective therapeutic agents for pancreatic cancer. In vitro and in vivo studies demonstrated that both compounds inhibited proliferation, caused cell cycle arrest, and induced apoptosis. They also both inhibited the growth of xenograft tumors without any host toxicity. Preliminary investigations into the mechanisms of action of the compounds suggest that their effects may be partially mediated by their inhibition of the MDM2 oncogene and related pathways. The data presented here support further evaluation of the ginsenosides for pancreatic cancer therapy.
Wang
Wei
W
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, and Comprehensive Cancer Center, University of Alabama at Birmingham, VH 113, Box 600, 1670 University Blvd., Birmingham, AL 35294, USA.
Rayburn
Elizabeth R
ER
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, and Comprehensive Cancer Center, University of Alabama at Birmingham, VH 113, Box 600, 1670 University Blvd., Birmingham, AL 35294, USA; Department of Gene Therapy, University of Alabama at Birmingham, Birmingham, AL, USA.
Zhao
Yuqing
Y
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, and Comprehensive Cancer Center, University of Alabama at Birmingham, VH 113, Box 600, 1670 University Blvd., Birmingham, AL 35294, USA; Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Wang
Hui
H
Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China.
Zhang
Ruiwen
R
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, and Comprehensive Cancer Center, University of Alabama at Birmingham, VH 113, Box 600, 1670 University Blvd., Birmingham, AL 35294, USA; Department of Gene Therapy, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: ruiwen.zhang@ccc.uab.edu.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000097669:Dammaranes
D000970:Antineoplastic Agents; D036145:Ginsenosides; D051736:Proto-Oncogene Proteins c-mdm2; D014315:Triterpenes; C529607:25-hydroxyprotopanaxadiol; C517965:25-methoxydammarane-3,12,20-triol; D000097669:Dammaranes; C497206:MDM2 protein, human