title: Inhibition effects of lamellarin D on human leukemia K562 cell proliferation and underlying mechanisms.
abstract: Lamellarin D (LamD) is a marine alkaloid with a pronounced cytotoxicity against a large panel of cancer cells, affecting cell growth and inducing apoptosis. However, the molecular mechanisms of action of this compound are poorly understood. In this study, the anticancer efficacy of LamD was investigated in human leukemia K562 cells. The results showed suppressed cell proliferation and induction of G0/G1-phase arrest,while expression of CDK1, and activity of smad3 and smad5 were reduced, but that of p27, p53 and STGC3 was increased. LamD induced cell apoptosis through activation of caspases-8/-3, inhibition of survivin and Bcl-2, suggesting that this compound may also act through a caspase-independent pathway. Moreover, LamD inhibited the secretion of TGF-β, IL-1β, IL-6, IL-8 and other inflammatory cytokines and the transcriptional activity of transcription factor NF-κB in human leukemia K562 cells. Taken together, our results suggest that LamD-mediated inhibition of leukemia cell proliferation may be related to the induction of apoptosis and the regulation of cell cycle, tumor- related gene expression and cytokine expression, which may provide a new way of thinking for the treatment leukemia.
authors.affiliation: Department of Pharmacology, Tianjin Children's Hospital, Tianjin, China E-mail : roylinvip1969@126.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003374:Coumarins / Q000494:pharmacology*; D005434:Flow Cytometry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology*; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings; D015850:Interleukin-6; D016209:Interleukin-8; D007546:Isoquinolines; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C455554:lamellarin D; D020169:Caspases