3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitor, Fluvastatin, as a Novel Agent for Prophylaxis of Renal Cancer Metastasis

Horiguchi, Akio; Sumitomo, Makoto; Asakuma, Junichi; Asano, Tomohiko; Hayakawa, Masamichi

doi:10.1158/1078-0432.ccr-04-1568

Cited by 90 publications

(83 citation statements)

References 24 publications

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“…In general, various cancers are sensitive to statin treatment (33)(34)(35). Similarly, ovarian cancer cells may be sensitive to simvastatin treatment (12).…”

Section: Discussionmentioning

confidence: 99%

Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma

Matsuura

Suzuki²,

Suzuki³

et al. 2010

Oncol Rep

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Abstract. Poor prognosis in ovarian clear cell carcinoma is associated with the expression of a defined set of proteins including osteopontin (OPN) and integrin. Statins, a family of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, are currently being investigated for the treatment and prevention of cancer. In this study, we investigated the effects of simvastatin on ovarian clear cell carcinoma (OCCC) cells in vitro and in vivo and elucidated the mechanism of drug action. Changes in OPN gene expression were determined by real-time RT-PCR, and an MTT assay was performed to determine effects on cell proliferation. Finally, a xenograft tumor model was constructed to evaluate the effects of simvastatin on cell proliferation and apoptosis in vivo. According to our experimental results, OPN is an important protein in OCCC. Simvastatin inhibited OCCC cell proliferation, and the inhibition rate was approximately 40% to 50% after treatment with 10 μM simvastatin for 48 h. In the xenograft studies, simvastatin treatment resulted in a significant growth inhibition. Furthermore, the mice treated with simvastatin survived significantly longer compared to the control groups. In conclusion, simvastatin has anticancer effects in vitro and in vivo. Further confirmation of the anticancer effects of statins in future studies will increase the scope for OCCC treatment.

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“…In general, various cancers are sensitive to statin treatment (33)(34)(35). Similarly, ovarian cancer cells may be sensitive to simvastatin treatment (12).…”

Section: Discussionmentioning

confidence: 99%

Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma

Matsuura

Suzuki²,

Suzuki³

et al. 2010

Oncol Rep

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show abstract

“…Horiguchi and colleagues demonstrated that oral fluvastatin, administered at the recommended doses for hypercholesterolemia, markedly suppressed metastasis in a mouse model of RCC. 60 Their in vitro data linked fluvastatin effects to the induction of cell arrest and apoptosis as well as to an inhibitory effect on angiogenesis and invasion. 60 In another study, Woodard and colleagues demonstrated that statins suppress activation of the mTOR pathway in RCC cells via inhibition of Akt activation.…”

Section: Statinsmentioning

confidence: 99%

“…60 Their in vitro data linked fluvastatin effects to the induction of cell arrest and apoptosis as well as to an inhibitory effect on angiogenesis and invasion. 60 In another study, Woodard and colleagues demonstrated that statins suppress activation of the mTOR pathway in RCC cells via inhibition of Akt activation. 61 Although, to our knowledge, there are no data yet to show whether statins can reduce cholesterol accumulation in RCC and whether that by itself has a tumour-suppressive effect, the data suggest a rationale to prospectively examine the role of statins in chemoprevention of primary RCC and against the potential recurrence of the disease following surgical removal of the primary tumour in an adjuvant setting.…”

Section: Statinsmentioning

confidence: 99%

Metabolic features of clear-cell renal cell carcinoma: mechanisms and clinical implications

Pinthus

Whelan

Gallino

et al. 2013

CUAJ

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Central to the malignant behaviour that endows cancer cells with growth advantage is their unique metabolism. Cancer cells can process nutrient molecules differently from normal cells and use it to overcome stress imposed on them by various therapies. This metabolic conversion is controlled by specific genetic mutations that are associated with activation of oncogenes and loss of tumour suppressor proteins. Understanding these processes is important as it can lead to the discovery of biomarkers that can predict the aggressiveness of the disease and its response to therapy, and even more importantly, to the development of novel therapeutics. A classic tumour in this respect is clear-cell renal cell carcinoma (RCC). In this review, we will begin with a brief summary of normal cellular bioenergetic pathways, which will be followed by a description of the characteristic metabolism of glucose and lipids in clear-cell RCC cells and its clinical implications. Data relating to the potential effect of dietary nutrients on RCC will also be reviewed along with potential therapies targeted at interrupting specific metabolic pathways in clear-cell RCC.

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“…24 Briefly, cells infected with L-GFP or L-NEP at MOI 10 for 48 h were trypsinized, and a cell suspension of 2 Â 10 5 cells in 500 ml of serum-free medium was added to the insert and 750 ml of medium containing 10% FCS was added to the lower chamber. Following incubation for 24 h at 371C, membranes were fixed and stained using Diff-Quik Stain Set (Dade Behring, Inc., Deerfield, IL), and the numbers of invaded cells were determined at 40-fold magnification in at least 10 fields of each well.…”

Section: Matrigel Invasion Assaymentioning

confidence: 99%

Lentiviral vector neutral endopeptidase gene transfer suppresses prostate cancer tumor growth

et al. 2007

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Neprilysin (neutral endopeptidase, NEP) is a cell surface peptidase whose expression is lost in approximately 50% of prostate cancers (PC). NEP normally functions to inactivate peptides such as bombesin and endothelin-1, and potentiates the effects of the PTEN tumor suppressor via a direct protein-protein interaction. NEP loss contributes to PC progression. We investigated the therapeutic efficacy of using a lentiviral vector system to restore NEP expression in PC cells. These experiments demonstrate that lentiviral NEP gene transfer is a novel targeted strategy for the treatment of NEP-deficient PC.

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3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitor, Fluvastatin, as a Novel Agent for Prophylaxis of Renal Cancer Metastasis

Abstract: Conclusions: Because our results suggest that fluvastatin may effectively inhibit in vitro tumor growth, invasion, angiogenesis, and metastasis of Renca cells, oral administration of fluvastatin could be a novel, safe, and effective agent for preventing metastasis of renal cancer.

Cited by 90 publications

References 24 publications

Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma

Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma

Metabolic features of clear-cell renal cell carcinoma: mechanisms and clinical implications

Lentiviral vector neutral endopeptidase gene transfer suppresses prostate cancer tumor growth

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