A new rexinoid, NRX194204, prevents carcinogenesis in both the lung and mammary gland

Karen Liby, Darlene B. Royce, Renee Risingsong, Charlotte R. Williams, Matthew Wood, Roshantha A. Chandraratna, Michael B. Sporn

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: We evaluated the anti-inflammatory and growth-inhibitory properties of the novel rexinoid NRX194204 (4204) in vitro and then tested its ability to prevent and/or treat experimental lung and estrogen receptor (ER)- negative breast cancer in vivo. Experimental Design: Incellculture studies, we measured the ability of 4204 to block the effects of lipopolysaccharide and induce apoptosis. For the lung cancer prevention studies, A/J mice were injected with the carcinogenvinyl carbamate and then fed 4204 (30-60 mg/kg diet) for 15 weeks, beginning 1 week after the administration of the carcinogen. For breast cancer prevention studies, mouse mammary tumor virus-neu mice were fed control diet or 4204 (20 mg/kg diet) for 50 weeks; for treatment, tumors at least 32 mm3 in size were allowed to form, and thenmice were fed control diet or 4204 (60mg/kg diet) for 4 weeks. Results: Low nanomolar concentrations of 4204 blocked the ability of lipopolysaccharide and tumor necrosis factor-α to induce the release of nitric oxide and interleukin 6 and the degradation of IKBα in RAW264.7 macrophage-like cells. In the A/J mouse model of lung cancer, 4204 significantly (P < 0.05) reduced the number and size of tumors on the surface of the lungs and reduced the total tumor volume per slide by 64% to 81% compared with the control group. Inmouse mammary tumor virus-neu mice, 4204 not only delayed the development of ER-negative mammary tumors in the prevention studies but also caused marked tumor regression (92%) or growth arrest (8%) in all of the mammary tumors when used therapeutically. Conclusions: The combined anti-inflammatory and anticarcinogenic actions of 4204 suggest that it is a promising new rexinoid that should be considered for future clinical trials.

Original languageEnglish (US)
Pages (from-to)6237-6243
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number20
DOIs
StatePublished - Oct 15 2007
Externally publishedYes

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Human Mammary Glands
Carcinogenesis
Diet
Lung
Breast Neoplasms
Mouse mammary tumor virus
Estrogen Receptors
Lipopolysaccharides
Lung Neoplasms
Anti-Inflammatory Agents
Neoplasms
Carbamates
Growth
Tumor Burden
Carcinogens
Interleukin-6
Nitric Oxide
Research Design
Tumor Necrosis Factor-alpha
Macrophages

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Liby, K., Royce, D. B., Risingsong, R., Williams, C. R., Wood, M., Chandraratna, R. A., & Sporn, M. B. (2007). A new rexinoid, NRX194204, prevents carcinogenesis in both the lung and mammary gland. Clinical Cancer Research, 13(20), 6237-6243. https://doi.org/10.1158/1078-0432.CCR-07-1342

A new rexinoid, NRX194204, prevents carcinogenesis in both the lung and mammary gland. / Liby, Karen; Royce, Darlene B.; Risingsong, Renee; Williams, Charlotte R.; Wood, Matthew; Chandraratna, Roshantha A.; Sporn, Michael B.

In: Clinical Cancer Research, Vol. 13, No. 20, 15.10.2007, p. 6237-6243.

Research output: Contribution to journalArticle

Liby, K, Royce, DB, Risingsong, R, Williams, CR, Wood, M, Chandraratna, RA & Sporn, MB 2007, 'A new rexinoid, NRX194204, prevents carcinogenesis in both the lung and mammary gland', Clinical Cancer Research, vol. 13, no. 20, pp. 6237-6243. https://doi.org/10.1158/1078-0432.CCR-07-1342
Liby, Karen ; Royce, Darlene B. ; Risingsong, Renee ; Williams, Charlotte R. ; Wood, Matthew ; Chandraratna, Roshantha A. ; Sporn, Michael B. / A new rexinoid, NRX194204, prevents carcinogenesis in both the lung and mammary gland. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 20. pp. 6237-6243.
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abstract = "Purpose: We evaluated the anti-inflammatory and growth-inhibitory properties of the novel rexinoid NRX194204 (4204) in vitro and then tested its ability to prevent and/or treat experimental lung and estrogen receptor (ER)- negative breast cancer in vivo. Experimental Design: Incellculture studies, we measured the ability of 4204 to block the effects of lipopolysaccharide and induce apoptosis. For the lung cancer prevention studies, A/J mice were injected with the carcinogenvinyl carbamate and then fed 4204 (30-60 mg/kg diet) for 15 weeks, beginning 1 week after the administration of the carcinogen. For breast cancer prevention studies, mouse mammary tumor virus-neu mice were fed control diet or 4204 (20 mg/kg diet) for 50 weeks; for treatment, tumors at least 32 mm3 in size were allowed to form, and thenmice were fed control diet or 4204 (60mg/kg diet) for 4 weeks. Results: Low nanomolar concentrations of 4204 blocked the ability of lipopolysaccharide and tumor necrosis factor-α to induce the release of nitric oxide and interleukin 6 and the degradation of IKBα in RAW264.7 macrophage-like cells. In the A/J mouse model of lung cancer, 4204 significantly (P < 0.05) reduced the number and size of tumors on the surface of the lungs and reduced the total tumor volume per slide by 64{\%} to 81{\%} compared with the control group. Inmouse mammary tumor virus-neu mice, 4204 not only delayed the development of ER-negative mammary tumors in the prevention studies but also caused marked tumor regression (92{\%}) or growth arrest (8{\%}) in all of the mammary tumors when used therapeutically. Conclusions: The combined anti-inflammatory and anticarcinogenic actions of 4204 suggest that it is a promising new rexinoid that should be considered for future clinical trials.",
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