title: Jaridonin, a novel ent-kaurene diterpenoid from Isodon rubescens, inducing apoptosis via production of reactive oxygen species in esophageal cancer cells.
abstract: Isodon rubescens, a Chinese herb, has been used as a folk, botanical medicine in China for inflammatory diseases and cancer treatment for many years. Recently, we isolated a new ent-kaurene diterpenoid, named Jaridonin, from Isodon rubescens. The chemical structure of Jaridonin was verified by infrared (IR), nuclear magnetic resonance (NMR), and mass spectrum (MS) data as well as X-ray spectra. Jaridonin potently reduced viabilities of several esophageal cancer cell lines, including EC109, EC9706 and EC1. Jaridonin treatment resulted in typical apoptotic morphological characteristics, increased the number of annexin V-positive staining cells, as well as caused a G2/M arrest in cell cycle progression. Furthermore, Jaridonin resulted in a significant loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, and then activation of Caspase-9 and -3, leading to activation of the mitochondria mediated apoptosis. Furthermore, these effects of Jaridonin were accompanied by marked reactive oxygen species (ROS) production and increased expression of p53, p21(waf1/Cip1) and Bax, whereas two ROS scavengers, N-acetyl-L-cysteine (LNAC) and Vitamin C, significantly attenuated the effects of Jaridonin on the mitochondrial membrane potential, DNA damage, expression of p53 and p21(waf1/Cip1) and reduction of cell viabilities. Taken together, our results suggest that a natural ent-kaurenoid diterpenoid, Jaridonin, is a novel apoptosis inducer and deserves further investigation as a new chemotherapeutic strategy for patients with esophageal cancer.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China.
authors.forename: Yong-Cheng
authors.initials: YC
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Ke
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zi
authors.forename: Wen
authors.initials: W
authors.lastname: Zhao
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Shi
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002681:China; D004249:DNA Damage; D045786:Diterpenes, Kaurane / Q000009:adverse effects / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020834:Ethnopharmacology; D016195:G2 Phase / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D037602:Isodon / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018515:Plant Leaves / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; C587044:jaridonin