Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells.
PC-SPES is an eight herbal mixture that was shown to have activity against prostate cancer. Recently, we purified oridonin from Rabdosia rubescens, one component of PC-SPES, by high performance liquid chromatography (HPLC). The ability of oridonin to inhibit the proliferation of cancer cells was examined by MTT assay. Oridonin effectively inhibited the proliferation of a wide variety of cancer cells including those from prostate (LNCaP, DU145, PC3), breast (MCF-7, MDA-MB231), non-small cell lung (NSCL) (NCI-H520, NCI-H460, NCI-H1299) cancers, acute promyelocytic leukemia (NB4), and glioblastoma multiforme (U118, U138) with ED50s ranging from 1.8 to 7.5 micro g/ml. TUNEL assay and cell cycle analysis showed that oridonin induced apoptosis and G0/G1 cell cycle arrest in LNCaP prostate cancer cells. In addition, expression of p21waf1 was induced in LNCaP and NCI-H520 cells in a p53-dependent manner. Interestingly, when p53 was suppressed by over-expression of E6 from human papilloma virus type 16 (HPV-16), these cells lost their sensitivity to oridonin-induced growth inhibition and apoptosis. Taken together, oridonin inhibited the proliferation of cancer cells via apoptosis and cell cycle arrest with p53 playing a central role in several cancer types which express the wild-type p53 gene. Oridonin may be a novel, adjunctive therapy for a large variety of malignancies and probably represents one of the major, active components of PC-SPES.
Ikezoe
Takayuki
T
Department of Internal Medicine, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. ikezoet@med.kochi-ms.ac.jp
Chen
Sophie S
SS
Tong
Xian-Jun
XJ
Heber
David
D
Taguchi
Hirokuni
H
Koeffler
H Phillip
HP
D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D016923:Cell Death; D002455:Cell Division; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D045786:Diterpenes, Kaurane; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D012097:Repressor Proteins; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493956:CDKN1A protein, human; D004396:Coloring Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004224:Diterpenes; D045786:Diterpenes, Kaurane; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C011959:oridonin; C022616:thiazolyl blue