title: Jolkinolide A and Jolkinolide B Inhibit Proliferation of A549 Cells and Activity of Human Umbilical Vein Endothelial Cells.
abstract: BACKGROUND Jolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities. MATERIAL AND METHODS We used different concentrations of JA and JB (20 μg/ml, 40 μg/ml, 60 μg/ml, 80 μg/ml, and 100 μg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers. In addition, we used conditional media from A549 cells (A549-CM) stimulated by either JA or JB in different concentrations to culture human umbilical vein endothelial cells (HUVECs). RESULTS We found that both JA and JB significantly inhibited the Akt-STAT3-mTOR signaling pathway and reduced the expression of VEGF in A549 cells, but JB exhibited more significant inhibitory effects than JA. The JB-stimulated A549 cell conditional media had a greater inhibitory effect on the proliferation and migration of HUVECs than did the conditional media of JA-stimulated A549 cells. This effect gradually increased with increasing concentrations of either type of Jolkinolide. CONCLUSIONS Our results suggest that JA and JB inhibited VEGF expression in A549 cells through the inhibition of the Akt-STAT3-mTOR signaling pathway, and directly inhibited the proliferation and migration of HUVECs. These findings are of great significance for the development of new plant-derived chemotherapy agents for the treatment of cancer.
authors.affiliation: Qigihar Institute of Medical and Pharmaceutical Sciences, Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland).|Department of Anatomy, Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland).
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Anatomy, Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland).
authors.forename: Shan-Qiang
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Qigihar Institute of Medical and Pharmaceutical Sciences, Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland).
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Qigihar Institute of Medical and Pharmaceutical Sciences, Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland).
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anatomy, Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland).
authors.forename: Yu-Xuan
authors.initials: YX
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland).
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Xie
authors.affiliation: Qigihar Institute of Medical and Pharmaceutical Sciences, Qiqihar Medical University, Qiqihar, Heilongjiang, China (mainland).
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Liu
mesh_terms: D000072283:A549 Cells; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D042461:Vascular Endothelial Growth Factor A; C057915:jolkinolide A; C057914:jolkinolide B; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases