NIK-333 inhibits growth of human T-cell leukemia virus type I-infected T-cell lines and adult T-cell leukemia cells in association with blockade of nuclear factor-κB signal pathway

Okudaira, Taeko; Tomita, Masaru; Uchihara, Jun-Nosuke; Matsuda, Takehiro; Ishikawa, Chie; Kawakami, Hiroyoshi; Masuda, Masato; Tanaka, Yuetsu; Ohshiro, Kazuiku; Takasu, Nobuyuki; Mori, Nozomu

doi:10.1158/1535-7163.mct-05-0434

Cited by 16 publications

(15 citation statements)

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“…HTLV-1-infected T-cells aberrantly expressed XIAP, which was consistent with previous studies [6], and exposure of these cells to MS-275 (3 or 6 μM, 48 h) prominently decreased levels of this anti-apoptotic protein (Fig 4A). Expression of p21 waf1 was not detectable in MT-1 and HUT102 cells ( Fig 4A); exposure of these cells to MS-275 (3 or 6 μM, 48 h) dramatically induced p21 waf1 levels (Fig 4A).…”

Section: Effect Of Hdacis On Cell Cycle and Apoptosis-related Proteinsupporting

confidence: 91%

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Histone deacetylase inhibitors induce growth arrest and apoptosis of HTLV-1-infected T-cells via blockade of signaling by nuclear factor κB

et al. 2008

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Section: Effect Of Hdacis On Cell Cycle and Apoptosis-related Proteinsupporting

confidence: 91%

“…ATL cells aberrantly express these anti-apoptotic proteins via NF-κB signaling, which is associated with the resistance of these cells to apoptosis mediated by anti-cancer agents [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitors induce growth arrest and apoptosis of HTLV-1-infected T-cells via blockade of signaling by nuclear factor κB

et al. 2008

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“…However further study is needed in order to elucidate whether combination use with arsenic trioxide is effective. Novel synthetic retinoid derivatives, such as NIK-333 96 and Am80 (Tamibarotene), 97 are potentially useful therapeutic agents against ATL.…”

Section: ) Retinoid Derivativesmentioning

confidence: 99%

Treatment of Adult T-cell Leukemia

Uozumi

2010

J Clin Exp Hematopathol

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Adult T-cell Leukemia (ATL) is an aggressive malignant disease of CD4 + T-cells associated with human T-cell leukemia virus type I (HTLV-I). Prognosis of ATL patients is directly correlated to the subtype of ATL. Treatment of the aggressive forms (acute and lymphoma types) of ATL remains inadequate, as most ATL patients receive conventional chemotherapy without stem cell rescue. At present, LSG15 is the standard chemotherapy for the treatment of aggressive ATL, but the efficacy of LSG15 in most patients is transient. To prolong median survival time, additional therapies for maintenance of complete response (CR) are needed after achieving CR by induction chemotherapy. Improved outcome after allogeneic stem cell transplantation (allo-SCT), despite a high incidence of graft-versus-host disease, has been reported. Thus, allogeneic bone marrow transplantation and allogeneic peripheral blood SCT may have great potential for eradication of HTLV-1 and cure of ATL. Recently, reduced-intensity conditioning stem cell transplantation was also reported to be effective for ATL. Although several issues, including selection criteria for patients and sources of stem cells remain to be resolved, allo-SCT may be considered as a treatment option for patients with aggressive ATL. To evaluate whether allo-SCT is more effective than the standard chemotherapy (LSG15) for aggressive ATL, an upfront phase II clinical trial of JCOG-LSG is now being planned. Novel innovative targeted strategies, such as antiretroviral therapy, arsenic trioxide, nuclear factor-kB inhibitors, proteasome inhibitors, histone deacetylase inhibitors, several monoclonal antibodies including anti-CC chemokine receptor 4, anti-folate, purine nucleotide phosphorylase inhibitor, mTOR (mammalian target of rapamycin) inhibitor, bendamustine, small molecule Bcl-2 inhibitors and Tax-targeted immunotherapy, should be promptly studied in order to develop curative treatments for ATL in the near future. 〔J Clin Exp Hematopathol 50(1) : 9-25, 2010〕

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“…[46][47][48] The effect of Bay 11-7082, dehydroxymethylepoxyquinomicin and NIK-333 on growth suppression of HTLV-I-infected T-cell lines occurred at an IC 50 of 2.5-5.0, 13-27 and 9.2-24.2 lM, respectively. On the other hand, IC 50 of hG9NC(null) ranged from 0.012 to 0.095 lM.…”

Section: R E T R a C T Ementioning

confidence: 99%

Retracted: A modified version of galectin‐9 suppresses cell growth and induces apoptosis of human T‐cell leukemia virus type I‐infected T‐cell lines

Okudaira

Hirashima

Ishikawa

et al. 2007

Intl Journal of Cancer

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ATL is a fatal malignancy of T lymphocytes caused by HTLV-I infection and remains incurable. Galectins are a family of animal lectins that function both extracellularly (by interacting with cell surface and extracellular matrix glycoproteins and glycolipids) and intracellularly (by interacting with cytoplasmic and nuclear proteins) to modulate signaling pathways. We found that protease-resistant galectin-9 by modification of its linker peptide, hG9NC(null), prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells. The suppression of cell growth was inhibited by lactose, but not by sucrose, indicating that b-galactoside binding is essential for hG9NC(null)-induced cell growth suppression. hG9NC(null) induced cell cycle arrest by reducing the expression of cyclin D1, cyclin D2, cyclin B1, Cdk1, Cdk4, Cdk6, Cdc25C and c-Myc, and apoptosis by reducing the expression of XIAP, c-IAP2 and survivin. Most of these genes are regulated by NF-jB, which plays a critical role in oncogenesis by HTLV-I. hG9NC(null) suppressed IjBa phosphorylation, resulting in suppression of NF-jB. Most importantly, treatment with hG9NC(null) (6.7 mg/kg injected intraperitoneally every day) reduced tumor formation from an HTLV-I-infected T-cell line when these cells were inoculated subcutaneously into SCID mice. Our results suggest that hG9NC(null) could be a suitable agent for the management of ATL. ' 2007 Wiley-Liss, Inc.Key words: galectin-9; HTLV-I; ATL; NF-kB; apoptosis ATL is a unique malignancy of mature CD4-positive T cells caused by HTLV-I. 1-3 ATL is subclassified into 4 subtypes: acute, lymphoma, chronic and smoldering. In the relatively indolent smoldering and chronic types, the median survival time is more than 2 years. However, at present, there is no accepted curative therapy for ATL and the condition often progresses to death with a median survival time of 13 months in aggressive ATL. 4 Chemotherapies that are specifically known to be active against other lymphoid malignancies are ineffective for treating aggressive forms of ATL. Death is usually due to severe infection or hypercalcemia. Therefore, the establishment of new therapeutic strategies for ATL is very important.Galectins are a family of soluble b-galactoside binding animal lectins. To date, 14 members of the galectin family have been identified. Each member exhibits diverse biological functions and many of them appear to function in cellular homeostasis through regulation of cell adhesion, cell proliferation, cell death and chemoattraction. [5][6][7][8][9] The members can be classified into 3 subtypes according to their structures. The prototype (galectin-1, -2, -7, -10 and -13) and chimera type (galectin-3) galectins have a single CRD and they usually form a noncovalent homodimer resulting in homobifunctional sugar binding activity. Tandem-repeat type galectins (galectin-4, -8, -9 and -12) have two CRDs, which generally show different sugar binding specificities, joined by a linker peptide. This heterobifunctional property makes them capable of cros...

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NIK-333 inhibits growth of human T-cell leukemia virus type I-infected T-cell lines and adult T-cell leukemia cells in association with blockade of nuclear factor-κB signal pathway

Cited by 16 publications

References 53 publications

Histone deacetylase inhibitors induce growth arrest and apoptosis of HTLV-1-infected T-cells via blockade of signaling by nuclear factor κB

Histone deacetylase inhibitors induce growth arrest and apoptosis of HTLV-1-infected T-cells via blockade of signaling by nuclear factor κB

Treatment of Adult T-cell Leukemia

Retracted: A modified version of galectin‐9 suppresses cell growth and induces apoptosis of human T‐cell leukemia virus type I‐infected T‐cell lines

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