Peridinin, a carotenoid, inhibits proliferation and survival of HTLV-1-infected T-cell lines

被引:19
作者
Ishikawa, Chie [1 ,2 ]
Jomori, Takahiro [3 ]
Tanaka, Junichi [3 ]
Senba, Masachika [4 ]
Mori, Naoki [1 ]
机构
[1] Univ Ryukyus, Grad Sch Med, Dept Microbiol & Oncol, 207 Uehara, Nishihara, Okinawa 9030215, Japan
[2] Univ Ryukyus, Div Hlth Sci, Transdisciplinary Res Org Subtrop & Isl Studies, Nishihara, Okinawa 9030213, Japan
[3] Univ Ryukyus, Dept Chem Biol & Marine Sci, Nishihara, Okinawa 9030213, Japan
[4] Nagasaki Univ, Inst Trop Med, Dept Pathol, Nagasaki 8528523, Japan
关键词
peridinin; adult T-cell leukemia; human T-cell leukemia virus type 1; nuclear factor-kappa B; Akt; NF-KAPPA-B; ONCOGENE PRODUCT TAX; X-LINKED INHIBITOR; VIRUS TYPE-I; DEACETYLATED PRODUCT; C-MYC; APOPTOSIS PROTEIN; LEUKEMIA; PHOSPHORYLATION; ACTIVATION;
D O I
10.3892/ijo.2016.3648
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 G(1), phase, while higher concentration induced apoptosis. Peridinin caused cleavage of caspase-3, -8 and -9. Peridinin significantly reduced the expression of G, 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-kappa B. Peridinin inhibited phosphorylation of I kappa B alpha, 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-kappa B 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.
引用
收藏
页码:1713 / 1721
页数:9
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