Abstract
We evaluated the effects of Bidens pilosa, a plant found in tropical and subtropical regions, and investigated the molecular pathways responsible for the anti-adult T-cell leukemia (ATL) effect. Water extracts of B. pilosa had growth suppressive effects on human T-cell leukemia virus type 1 (HTLV-1)-infected T-cell lines and ATL cells. B. pilosa extracts arrested cells in G1 cell cycle and induced apoptosis of HTLV-1-infected T-cell lines. B. pilosa extracts inhibited also the phosphorylation of IκB kinase β and IκBα, and NF-κB-DNA binding, in conjunction with reduction of expression of proteins involved in G1/S cell cycle transition and suppression of apoptosis. Reactive oxygen species played a role in B. pilosa-mediated suppression of NF-κB activity. B. pilosa extracts also inhibited the expression of JunB and JunD, resulting in suppression of AP-1-DNA binding. In animals harboring tumors of HTLV-1-infected T-cell origin, treatment with B. pilosa extracts suppressed tumor growth. Our results suggest that B. pilosa is a potentially useful medicinal plant for treatment of ATL.
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology*
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Antineoplastic Agents, Phytogenic / therapeutic use
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Apoptosis / drug effects
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Bidens*
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Caffeic Acids / pharmacology
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Caspases / metabolism
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Cell Cycle / drug effects
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Cell Line
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Drugs, Chinese Herbal / pharmacology*
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Drugs, Chinese Herbal / therapeutic use
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Enzyme Activation
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Human T-lymphotropic virus 1 / drug effects
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Human T-lymphotropic virus 1 / physiology
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism
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Leukemia-Lymphoma, Adult T-Cell / drug therapy*
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Leukemia-Lymphoma, Adult T-Cell / pathology
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Leukemia-Lymphoma, Adult T-Cell / virology
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NF-kappa B / metabolism
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Reactive Oxygen Species / metabolism
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Signal Transduction / drug effects
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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T-Lymphocytes / virology
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Transcription Factor AP-1 / metabolism
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Virus Replication / drug effects
Substances
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Antineoplastic Agents, Phytogenic
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Caffeic Acids
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Drugs, Chinese Herbal
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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Reactive Oxygen Species
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Transcription Factor AP-1
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plant extract, Bidens pilosa
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Caspases
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caffeic acid