Inhibition of breast cancer metastasis to the lungs with UBS109

• Type of Material: Article
• Authors: Mamoru Shoji, Emory University; Wei Qian, Emory University; P Nagaraju Ganji, Emory University; Daniel Brat, Emory University; Danielle Pessolano, Charles River Laboratories, Inc.; Rick Luzietti, Charles River Laboratories, Inc.; Spandan Chennamadhavuni, Emory University; Masayoshi Yamaguchi, Emory University; Lily Yang, Emory University; Dennis Liotta, Emory University
• Language: English
• Date: 2018-11-01
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: Shoji et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.26302
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 9
• Issue: 90
• Start Page: 36102
• End Page: 36109
• Grant/Funding Information: 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; lung metastases; bone metastasis; UBS109; breast cancer
• Research Categories: Health Sciences, Pathology; Health Sciences, Oncology

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.