A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line

Shinoda, Kinya; Shibuya, Masabumi; Hibino, Suguru; Ono, Yasushi; Matsuda, Kuniko; Takemura, Akihiro; Zou, Datong; Kokubo, Yutaka; Takechi, Akiko; Kudoh, Shoji

doi:10.3892/ijo.22.2.281

Cited by 12 publications

(11 citation statements)

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“…For example, BMS-275291 is a potent inhibitor (nM) of the activities of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-14 and inhibits tumor angiogenesis and metastasis in experimental models [130]. Another MMP-2 and MMP-9 inhibitor, FYK-1388, has also shown the same antimetastatic effect [131]. Inhibition of MMP-1 using RNAi approach also reduces melanoma angiogenesis and metastasis [132].…”

Section: Invasion Migration and Angiogenesis-vegf And Mmpsmentioning

confidence: 96%

Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis

Shu

Cheung

Khor

et al. 2010

Cancer Metastasis Rev

216

153

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Carcinogenesis is a multi-step process which could be prevented by phytochemicals. Phytochemicals from dietary plants and other plant sources such as herbs are becoming increasingly important sources of anticancer drugs or compounds for cancer chemoprevention or adjuvant chemotherapy. Phytochemicals can prevent cancer initiation, promotion, and progression by exerting anti-inflammatory and anti-oxidative stress effects which are mediated by integrated Nrf2, NF-kappaB, and AP-1 signaling pathways. In addition, phytochemicals from herbal medicinal plants and/or some dietary plants developed in recent years have been shown to induce apoptosis in cancer cells and inhibition of tumor growth in vivo. In advanced tumors, a series of changes involving critical signaling molecules that would drive tumor cells undergoing epithelial-mesenchymal transition and becoming invasive. In this review, we will discuss the potential molecular targets and signaling pathways that mediate tumor onset and metastasis. In addition, we will shed light on some of the phytochemicals that are capable of targeting these signaling pathways which would make them potentially applicable to cancer chemoprevention, treatment and control of cancer progression.

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Section: Invasion Migration and Angiogenesis-vegf And Mmpsmentioning

confidence: 96%

Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis

Shu

Cheung

Khor

et al. 2010

Cancer Metastasis Rev

216

153

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“…MMP-2 [104] or MMP-13 [105], resulted in significant progress in inhibition of metastasis in the experimental and spontaneous animal models. Anti-tumor effects of the gelatinase-specific inhibitor FYK-1388 was shown in experimental lung metastasis of HT-1080 fibrosarcoma [106]. Significant inhibition of breast cancer metastases in brain was achieved in a rat model when animals were treated with a synthetic inhibitor (PD 166793) [107].…”

Section: Mmp Inhibition Targeting Angiogenesismentioning

confidence: 98%

Matrix metalloproteinases and tumor metastasis

Deryugina

Quigley

2006

Cancer Metastasis Rev

1,734

1,376

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Functions of individual matrix metalloproteinases (MMPs) differentially expressed by tumor cells and stromal cells, are finely regulated by their spatial as well as temporal interactions with distinct cellular and extracellular components of the tumor microenvironment and also distant pre-metastatic sites. Certain aspects of MMP involvement in tumor metastasis such as tumor-induced angiogenesis, tumor invasion, and establishment of metastatic foci at the secondary site, have received extensive attention that resulted in an overwhelming amount of experimental and observational data in favor of critical roles of MMPs in these processes. In particular, dependency of tumor angiogenesis on the activity of MMPs, especially that of MMP-9, renders this step possibly the most effective target of synthetic MMP inhibitors. MMP functioning in other stages of metastasis, including the escape of individual tumor cells from the primary tumor, their intravasation, survival in circulation, and extravasation at the secondary site, have not yet received enough consideration, resulting in insufficient or controversial data. The major pieces of evidence that are most compelling and clearly determine the role and involvement of MMPs in the metastatic cascade are provided by molecular genetic studies employing knock-out or transgenic animals and tumor cell lines, modified to overexpress or downregulate a specific MMP. Findings from all of these studies implicate different functional mechanisms for both tumor and stromal MMPs during distinct steps of the metastatic cascade and indicate that MMPs can exhibit pro-metastatic as well as anti-metastatic roles depending on their nature and the experimental setting. This dual function of individual MMPs in metastasis has become a major focus of this review.

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“…FYK-1388 is a novel broad MMP inhibitor, which blocks the activity of MMP-1, -2, -3, -7, -9, -13 and -14 [159]. FYK-1388 is especially effective towards MMP-2 and MMP-9 and it has been shown to inhibit experimental lung metastasis in a nude mouse model [159].…”

Section: Nonpeptidic Inhibitorsmentioning

confidence: 99%

Matrix Metalloproteinases as Therapeutic Targets in Cancer

Vihinen

Ala-aho²,

Kähäri

2005

CCDT

262

210

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Degradation of extracellular matrix is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumor tissue or serum of patients with advanced cancer, and their role as prognostic indicators in cancer has been widely examined. In addition, therapeutic intervention in tumor growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors (MMPIs) are in clinical cancer trials. Even though results of the first clinical trials in advanced cancer have been mostly disappointing, there are also positive results. Recent observations show, that certain MMPs limit tumor growth. Therefore, identification of proper MMPs for therapeutic intervention with array-based molecular classifications of tumors and targeting these with more specific MMPIs in combination with conventional chemotherapy is expected to provide a feasible approach for cancer therapy. MMPIs represent a totally different therapeutic modality from proven anti-cancer drugs and thus traditional approaches to evaluate drug efficiency cannot be used without modification. In this review, we discuss the current view on the feasibility of MMPs as targets for therapeutic intervention in cancer.

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A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line

Cited by 12 publications

References 0 publications

Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis

Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis

Matrix metalloproteinases and tumor metastasis

Matrix Metalloproteinases as Therapeutic Targets in Cancer

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