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 (Cmax) 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.