Chemoprevention of LA7-induced mammary tumor growth by SM6Met, a well-characterized cyclopia extract
Date
2018
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers
Abstract
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 wellcharacterized
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 17b-estradiol and standard-of-care (SOC) endocrine therapies, such as tamoxifen
(TAM), letrozole (LET), and fulvestrant (FUL). Tumor growth was observed in the tumorvehicle
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 17b-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 17b-estradiol treatment groups. Alterations in the lipid profiles
were also observed in the 17b-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.
Keywords: chemoprevention, Cyclopia, mammary tumor, phytoestrogen, tamoxifen, letrozole, fulvestrant
Description
CITATION: Oyenihi. O. R. et al. 2018. Chemoprevention of LA7-induced mammary tumor growth by SM6Met, a well-characterized cyclopia extract. Frontiers in Pharmacology, 9:650, doi:10.3389/fphar.2018.00650.
The original publication is available at https://www.frontiersin.org
The original publication is available at https://www.frontiersin.org
Keywords
Breast -- Cancer -- Alternative treatment, Mammary tumor -- Chemoprevention, Cyclopia, Phytoestrogens
Citation
Oyenihi. O. R. et al. 2018. Chemoprevention of LA7-induced mammary tumor growth by SM6Met, a well-characterized cyclopia extract. Frontiers in Pharmacology, 9:650, doi:10.3389/fphar.2018.00650.