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

摘要

Over the past two decades, bioactive natural compounds havenbeen shown to be a plausible adjunct to the treatment of breastncancer, the second leading cause of cancer death among Americannwomen. This study was designed to investigate the effects of ur-nsolic acid (UA), a pentacyclic triterpene found in many foods andnherbs, in amodel of postmenopausal breast cancer.OvariectomizednC57BL/6 mice (n = 40) were randomized to receive control dietn(AIN-93G) or diet supplemented with UA at 1 of 3 doses (wt/wt):n0.05%, 0.10%, or 0.25%(≈54, 106, or 266 mg/kg body weight/day,nrespectively). After 3 wk, syngeneic MMTV-Wnt-1 mammary tu-nmor cells were injected in the mammary fat pad, and mice contin-nued on their respective diets for 5more wk. All UA doses decreasedntumor cell proliferation, as assessed by Ki67 immunostaining; nev-nertheless, UA at 0.10%was most effective in inhibiting tumor takenand decreasing tumor final tumor size. Modulation of Akt/mTORnsignaling and induction of apoptosis appeared to mediate these ef-nfects on tumor growth.UApotently disrupted cell cycle progressionnand induced necrosis in a clonal MMTV-Wnt-1 mammary tumorncell line in vitro. This study supports the potential of UA as annantitumorigenic agent.