title: B-cell lymphoma-2 over-expression protects δ-elemene-induced apoptosis in human lung carcinoma mucoepidermoid cells via a nuclear factor kappa B-related pathway.
abstract: δ-Elemene, an antitumor component, is a chemical compound isolated from Curcuma wenyujin, a Chinese traditional herb. We examined whether δ-elemene could affect apoptosis in human lung carcinoma mucoepidermoid NCI-H292 cells, and test whether and how the over-expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma extra large (Bcl-xL) could off-set the effect of δ-elemene on cell growth. The result demonstrated that δ-elemene significantly induced apoptosis of NCI-H292, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, DNA fragmentation measurement, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. Treatment of NCI-H292 with δ-elemene increased both p38 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthese (iNOS) levels, suggesting these two molecules maybe relate to the apoptotic effect of δ-elemene. The cells with Bcl-2 or Bcl-xL over-expression showed an elevation of nuclear factor kappa B (NF-kappa B) activity, accompanying a significant reduction of δ-elemene-induced apoptosis. Furthermore, inhibition of NF-kappa B by IkBαSR, which is a powerful inhibitor of NF-kappa B, restored the ability of δ-elemene to induce apoptosis in the cells transfected with Bcl-2. These data strongly indicated that the apoptotic effect of δ-elemene on NCI-H292 was closely associated with the activity of NF-kappa B, which was up-regulated by Bcl-2 and Bcl-xL. In conclusion, δ-elemene induced apoptosis in NCI-H292 cells. The apoptotic effect of δ-elemene could be significantly offset by over-expression of either Bcl-2 or Bcl-xL. Bcl-2 and Bcl-xL were able to increase the activity of NF-kappa B, which was a known anti-apoptotic molecule in human lung cancer cells.
authors.affiliation: The Sixth Affiliated Hospital, Sun Yat-Sen University, Guanzhou, Guangdong 510655, P. R. China.
authors.forename: Chun Ying
authors.initials: CY
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Ying
authors.forename: Qing Chun
authors.initials: QC
authors.lastname: Ni
authors.forename: Xue Diao
authors.initials: XD
authors.lastname: Pan
authors.forename: Jin Hua
authors.initials: JH
authors.lastname: Dong
authors.forename: Karen
authors.initials: K
authors.lastname: Li
authors.forename: Xi Sha
authors.initials: XS
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D018277:Carcinoma, Mucoepidermoid / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D030024:Curcuma / Q000737:chemistry*; D053938:DNA Fragmentation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D051020:bcl-X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; D051020:bcl-X Protein; C038905:elemene; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases