TY - JOUR
T1 - Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer
AU - De Angel, Rebecca E.
AU - Smith, Sarah M.
AU - Glickman, Randolph D.
AU - Perkins, Susan N.
AU - Hursting, Stephen D.
N1 - Funding Information:
The authors would like to thank Richard Salinas for his valuable advice on cell cycle and apoptosis analyses. This work was supported in part by funds received from a UT System grant to the Texas Consortium for Chronic Disease Prevention (RDG) and grants to S. D. Hursting from the Breast Cancer Research Foundation and from the U.S. Department of Defense Congressionally Directed Breast Cancer Research Program (BC 053292).
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
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U2 - 10.1080/01635581.2010.492092
DO - 10.1080/01635581.2010.492092
M3 - Article
C2 - 21058195
AN - SCOPUS:78249242752
VL - 62
SP - 1074
EP - 1086
JO - Nutrition and Cancer
JF - Nutrition and Cancer
SN - 0163-5581
IS - 8
ER -