Breast cancer (BC) is the leading cause of
cancer-related deaths in women.
Chemoprevention of BC by using
plant extracts is gaining attention. SM6Met, a well-characterized extract of
Cyclopia subternata with reported selective
estrogen receptor subtype activity, has shown
tumor suppressive effects in a chemically induced BC model in rats, which is known to be
estrogen responsive. However, there is no information on the
estrogen sensitivity of the relatively new orthotopic model of LA7 cell-induced mammary
tumors. In the present study, the potential chemopreventative and side-effect profile of SM6Met on LA7 cell-induced
tumor growth was evaluated, as was the effects of 17β-estradiol and standard-of-care (SOC) endocrine
therapies, such as
tamoxifen (TAM),
letrozole (LET), and
fulvestrant (FUL).
Tumor growth was observed in the
tumor-vehicle control group until day 10 post
tumor induction, which declined afterward on days 12-14. SM6Met suppressed
tumor growth to the same extent as TAM, while LET, but not FUL, also showed substantial anti-
tumor effects. Short-term 17β-estradiol treatment reduced
tumor volume on days prior to day 10, whereas
tumor promoting effects were observed during long-term treatment, which was especially evident at later time points. Marked elevation in
serum markers of liver injury, which was further supported by histological evaluation, was observed in the vehicle-treated
tumor control, TAM, LET, and long-term 17β-estradiol treatment groups. Alterations in the
lipid profiles were also observed in the 17β-estradiol treatment groups. In contrast, SM6Met did not augment the increase in serum levels of liver injury
biomarkers caused by
tumor induction and no effect was observed on
lipid profiles. In summary, the results from the current study demonstrate the chemopreventative effect of SM6Met on mammary
tumor growth, which was comparable to that of TAM, without eliciting the negative side-effects observed with this SOC endocrine
therapy. Furthermore, the results of this study also showed some responsiveness of LA7-induced
tumors to
estrogen and SOC endocrine
therapies. Thus, this model may be useful in evaluating potential endocrine
therapies for
hormone responsive BC.