title: Jolkinolide B induces apoptosis in MCF-7 cells through inhibition of             the PI3K/Akt/mTOR signaling pathway.
abstract: The aim of this study was to explore the molecular mechanisms of jolkinolide B             (JB), which is extracted from the root of Euphorbia fischeriana Steud. In this             study, we found that JB, a diterpenoid from the traditional Chinese medicinal             herb, strongly inhibited the PI3K/Akt/mTOR signaling pathway. Furthermore, we             evaluated the effects of JB on the proliferation and apoptosis of MCF-7 human             breast cancer cells. Our results showed significant induction of apoptosis in             MCF-7 cells incubated with JB. The viability of the MCF-7 cells was assessed by             MTT assay. Flow cytometry was used to detect apoptosis and cell cycle analysis.             Transmission electron microscopy (TEM) analysis was used to observe cell morphology.             MCF-7 cells were subcutaneously inoculated into nude mice to study the in vivo             antitumor effects of JB. The growth of MCF-7 cells was inhibited and arrested             in the S phase by JB. The data showed significantly decreased tumor volume and             weight in nude mice inoculated with MCF-7 cells. In addition, treatment with JB             was able to induce downregulation of cyclinD1, cyclinE, mTOR, p-PI3K and p-Akt,             and upregulation of PTEN and p-eIF4E. Collectively, JB-induced apoptosis of MCF-7             cells occurs through the PI3K/Akt/mTOR signaling pathway. Furthermore, the PI3K/Akt             signaling cascade plays a role in the induction of apoptosis in JB-treated cells.             These observations suggest that JB may have therapeutic applications in the treatment             of cancer.
authors.affiliation: Department of Immunology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, PR China.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Xu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Chen
authors.forename: Jin-Cai
authors.initials: JC
authors.lastname: Hou
authors.forename: Feng-Xia
authors.initials: FX
authors.lastname: Du
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C057914:jolkinolide B; C546842:MTOR protein, human; C494929:PTEN protein, human