Antitumor efficacy of FK228, a novel histone deacetylase inhibitor, depends on the effect on expression of angiogenesis factors

Sasakawa, Yuka; Naoe, Yoshinori; Noto, Takahisa; Inoue, Takeshi; Sasakawa, Tatsuya; Matsuo, Makoto; Manda, Toshitaka; Mutoh, Seitaro

doi:10.1016/s0006-2952(03)00411-8

Cited by 81 publications

(58 citation statements)

References 40 publications

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“…Overexpression of basic fibroblast growth factor (40) and VEGF (41) has been found in the tissue, serum, and urine of patients with bladder cancer and also has been associated with disease progression. HDAC inhibitors have been recently shown to inhibit endothelial cell migration, invasion, vascular sprouting in vitro, and vasculature formation in animal models of cancer (42)(43)(44). Our data show that SAHA inhibited tumor growth by inhibiting angiogenesis and its marker such as VEGF and its effects on angiogenesis were further enhanced in the presence of TRAIL.…”

Section: Cip1supporting

confidence: 50%

Suberoylanilide hydroxamic acid (Zolinza/vorinostat) sensitizes TRAIL-resistant breast cancer cells orthotopically implanted in BALB/c nude mice

Shankar

Davis

Singh

et al. 2009

Molecular Cancer Therapeutics

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The purpose of this study was to examine whether histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; Zolinza/vorinostat) could sensitize tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant breast carcinoma in vivo. BALB/c nude mice were orthotopically implanted with TRAIL-resistant MDA-MB-468 cells and treated i.v. with SAHA, TRAIL, or SAHA followed by TRAIL for four times during first 3 weeks. The effects of drugs on tumor growth and markers of apoptosis, metastasis, and angiogenesis were examined. SAHA sensitized TRAIL-resistant xenografts to undergo apoptosis through multiple mechanisms. Whereas TRAIL alone was ineffective, SAHA inhibited growth of MDA-MB-468 xenografts in nude mice by inhibiting markers of tumor cell proliferation, angiogenesis, and metastasis and inducing cell cycle arrest and apoptosis. The sequential treatment of nude mice with SAHA followed by TRAIL was more effective in inhibiting tumor growth, angiogenesis, and metastasis and inducing apoptosis than SAHA alone, without overt toxicity. Treatment of nude mice with SAHA resulted in down-regulation of nuclear factor-κB and its gene products (cyclin D1, Bcl-2, Bcl-X L , vascular endothelial growth factor, hypoxia-inducible factor-1α, interleukin-6, interleukin-8, matrix metalloproteinase-2, and matrix metalloproteinase-9) and up-regulation of DR4, DR5, Bak, Bax, Bim, Noxa, PUMA, p21 CIP1 , tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in tumor cells. Furthermore, control mice showing increased rate of tumor growth had increased numbers of CD31 + or von Willebrand factor-positive blood vessels and increased circulating vascular endothelial growth factor receptor 2-positive endothelial cells compared with SAHA-treated or SAHA plus TRAIL-treated mice. In conclusion, sequential treatment with SAHA followed by TRAIL may target multiple pathways in tumor progression, angiogenesis, and metastasis and represents a novel therapeutic approach to treat breast cancer. [Mol Cancer Ther 2009;8(6):1596-605]

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Section: Cip1supporting

confidence: 50%

Suberoylanilide hydroxamic acid (Zolinza/vorinostat) sensitizes TRAIL-resistant breast cancer cells orthotopically implanted in BALB/c nude mice

Shankar

Davis

Singh

et al. 2009

Molecular Cancer Therapeutics

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“…FK228 causes histone acetylation of angiogenesis factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and has a suppressive effect on their expression, which suggests that the effect on the expression of angiogenesis factors is important for the antitumor efficacy of FK228 (42)(43)(44).…”

Section: Mechanisms Of Hdac Inhibitionmentioning

confidence: 99%

Histone deacetylase inhibitors: A novel target of anticancer therapy (Review)

Kouraklis¹,

Theocharis²

2006

Oncol Rep

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Abstract. Accumulating evidence suggests that the acetylation and deacetylation of histones play significant roles in transcriptional regulation of eukaryotic cells. The balance between acetylation and deacetylation is an important factor in regulating gene expression and is thus linked to the control of cell fate. The histone deacetylase inhibitors (HDIs) including the hydroxamic acids, such as suberoylanilide hydroxamic acid and pyroxamide, the benzamides MS-275 and CI-994 and the butyrate derivative 4-PBA are a new class of anti-neoplastic agents currently being evaluated in clinical trials. Moreover, new synthetic HDIs have been used recently in phase I and II clinical trials. Over the next few years experts believe that as first generation HDIs produce clinical benefits and second generation inhibitors are rationally designed with improved specificity, this class of drugs will emerge as a new way of cancer treatment. The first clinical studies have shown that histone hyperacetylation can be achieved safely in humans and that treatment of cancer with such agents seems to become possible. The use of HDIs, probably in association with classical chemotherapy drugs or in combination with DNA-demethylating agents, could be promising for cancer patients. Further evaluation is needed to establish the clinical activity of combination therapy using HDIs with cytotoxic drugs or differentiation induced agents.

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“…This hypothesis is consistent with the prior literature showing that depsipeptide preferentially affects tumor cells when compared to normal cells. 1,9,15 Having determined that i.v. co-injection of depsipeptide can significantly increase the efficiency of PEI:DNAbased gene delivery, we then assessed whether it also alters HDAC activity in relevant tissues of injected mice.…”

Section: Role Of Depsipeptide In Transfection Y Liu Et Almentioning

confidence: 99%

“…Depsipeptide differentially affects tumor cells versus normal cells. 4,14,15 Therefore, we assessed whether i.v. co-injection of depsipeptide with PEI:DNA complexes encoding the wild-type human p53 gene produced differential effects on human p53 expression in metastatic tumors versus in adjacent normal cells within tumor-bearing mice.…”

Section: Introductionmentioning

confidence: 99%

Systemic co-administration of depsipeptide selectively targets transfection enhancement to specific tissues and cell types

et al. 2006

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Antitumor efficacy of FK228, a novel histone deacetylase inhibitor, depends on the effect on expression of angiogenesis factors

Cited by 81 publications

References 40 publications

Suberoylanilide hydroxamic acid (Zolinza/vorinostat) sensitizes TRAIL-resistant breast cancer cells orthotopically implanted in BALB/c nude mice

Suberoylanilide hydroxamic acid (Zolinza/vorinostat) sensitizes TRAIL-resistant breast cancer cells orthotopically implanted in BALB/c nude mice

Histone deacetylase inhibitors: A novel target of anticancer therapy (Review)

Systemic co-administration of depsipeptide selectively targets transfection enhancement to specific tissues and cell types

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