Antitumor Effects of Ursolic Acid in a Mouse Model of Postmenopausal Breast Cancer

Abstract

Over the past two decades, bioactive natural compounds have been shown to be a plausible adjunct to the treatment of breast cancer, the second leading cause of cancer death among American women. This study was designed to investigate the effects of ursolic acid (UA), a pentacyclic triterpene found in many foods and herbs, in a model of postmenopausal breast cancer. Ovariectomized C57BL/6 mice (n = 40) were randomized to receive control diet (AIN-93G) or diet supplemented with UA at 1 of 3 doses (wt/wt): 0.05%, 0.10%, or 0.25% (≈54, 106, or 266 mg/kg body weight/day, respectively). After 3 wk, syngeneic MMTV-Wnt-1 mammary tumor cells were injected in the mammary fat pad, and mice continued on their respective diets for 5 more wk. All UA doses decreased tumor cell proliferation, as assessed by Ki67 immunostaining; nevertheless, UA at 0.10% was most effective in inhibiting tumor take and decreasing tumor final tumor size. Modulation of Akt/mTOR signaling and induction of apoptosis appeared to mediate these effects on tumor growth. UA potently disrupted cell cycle progression and induced necrosis in a clonal MMTV-Wnt-1 mammary tumor cell line in vitro. This study supports the potential of UA as an antitumorigenic agent.