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Author Notes:

Correspondence to: Mamoru Shoji, email: mshoji@emory.edu

We are grateful to It's the Journey, Inc., for financial support.

We thank Anthea Hammond PhD, Department of Hematology and Medical Oncology at Emory University for editorial assistance.

The author(s) confirm that this article content has no conflicts of interest.

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Research Funding:

This research was supported by the It's the Journey, Inc. [MS, MY, SCM], the National Institutes of Health (NIH) grant R21CA82995-01A1, 1 R21 CA139035-01A1 [MS, DJB], the U.S. Department of Defense, Division of U.S. Army DAMD17-00-1-0241 and W81XWH-08-1-0494 [MS, DCL), and the Emory Institute for Drug Development (SCM, DCL).

Keywords:

  • MACs
  • UBS109
  • bone metastasis
  • breast cancer
  • lung metastases

Inhibition of breast cancer metastasis to the lungs with UBS109

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Journal Title:

Oncotarget

Volume:

Volume 9, Number 90

Publisher:

, Pages 36102-36109

Type of Work:

Article | Final Publisher PDF

Abstract:

Synthetic monocarbonyl analogs of curcumin (MACs) are cytotoxic against several cancers including head and neck cancer, pancreatic cancer, colon cancer, and breast cancer. Mechanisms of action include depolarization of the mitochondrial membrane potential and inhibition of NF-κB, leading to apoptosis. We previously demonstrated that UBS109 (MAC), has preventive effects on bone loss induced by breast cancer cell lines. We determined whether UBS109 could inhibit and prevent lung metastasis, since lung metastasis of breast cancer is a major problem in addition to bone metastasis. A breast cancer lung metastasis (colonization) model was created by injection of breast cancer cells MDA-MB-231 into the tail vein of athymic nude mice, nu/nu. Animals were treated with vehicle or UBS109 at 5 or 15 mg/kg body weight by intraperitoneal injection once daily 5 days a week for 5 weeks. UBS109 at 15 mg/kg significantly inhibited lung metastasis/colonization as demonstrated by reduced lung weight consisting of tumor nodules. The body weight of animals treated with UBS109 15 mg/kg remained the same as in the other groups. UBS109 killed completely (100%) MDA-MB-231 breast cancer cells at 1.25 μM in a cytotoxicity assay in vitro. UBS109 15 mg/kg i.p. showed a maximal blood concentration (C max ) of 432 ± 387 ng/mL at 15 min post injection. This is approximately 1.5 ng/ml in the blood of mice and equals 1.5 μM of UBS109. These in vitro and in vivo results are consistent with each other.

Copyright information:

Shoji et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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