title: Peridinin, a carotenoid, inhibits proliferation and survival of HTLV-1-infected T-cell lines.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) causes either adult T-cell leukemia (ATL) or chronic inflammatory disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis. These diseases are not curable as yet; therefore new agents for treatment and prevention are needed. Carotenoids are natural plant compounds with anti-carcinogenic activities. Peridinin is one of the most abundant carotenoids found in nature. Based on a series of past experiments, here we investigated the effects of peridinin extracted from Okinawan coral Isis hippuris on the proliferation and survival of HTLV-1-infected T-cell lines. The results of water-soluble tetrazolium-8 assay indicated that peridinin dose-dependently inhibits cell proliferation and viability of HTLV-1-infected T-cell lines. Flow cytometry showed that low concentration of peridinin induced cell cycle arrest at G1 phase, while higher concentration induced apoptosis. Peridinin caused cleavage of caspase-3, -8 and -9. Peridinin significantly reduced the expression of G1 cell cycle regulators, including cyclin D1, cyclin D2, CDK4, CDK6 and c-Myc, and anti-apoptotic proteins, including survivin, XIAP and Bcl-2, in a dose-dependent manner. Peridinin suppressed DNA binding of NF-κB. Peridinin inhibited phosphorylation of IκBα, RelA, Akt and p70 S6 kinase, and reduced protein expression level of 3-phosphoinositide-dependent protein kinase 1. Thus, peridinin exerts its anti-proliferative and pro-apoptotic effects by suppressing NF-κB and Akt signaling in HTLV-1-infected T cells. Peridinin also reduced tumor growth in mice harboring ATL xenograft tumors. The results suggested that peridinin is a potentially suitable therapeutic agent against HTLV-1-associated diseases.
authors: Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
authors: Chie
authors: C
authors: Ishikawa
authors: Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan.
authors: Takahiro
authors: T
authors: Jomori
authors: Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan.
authors: Junichi
authors: J
authors: Tanaka
authors: Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
authors: Masachika
authors: M
authors: Senba
authors: Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
authors: Naoki
authors: N
authors: Mori
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002338:Carotenoids / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D015490:HTLV-I Infections / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects*; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D014407:Tumor Cells, Cultured
chemical_list: C016040:peridinin; D002338:Carotenoids