Chemoprevention of LA7-Induced Mammary Tumor Growth by SM6Met, a Well-Characterized Cyclopia Extract

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 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.

Promising Anticancer Potential of Herbal Compounds against Breast Cancer: A Systemic Review

“…In another study, the extracts of Cyclopiasubternata reduced the volume of mammary tumor at the same rate as tamoxifen in an orthotopic rat model. Notably, in animals no side effects of tamoxifen and letrozole were reported 110 . The in vivo anticancer effects of plant derived foods against mammary carcinoma were also demonstrated by several recently published papers 14,111 .…”

Downregulation of Stemness Genes and Induction of Necrosis in Rat LA7 Cancer Stem Cells Induced Tumors Treated with Starved Fibroblasts Culture Supernatant

“…i.e., vimentin. We also considered the LA7 cells as estrogen receptor positive cells based on a previous report (23); therefore, we used this antigen in our IHC panel. As it can be realized from Figure 4, the LA7 cells transformed to Ki67 + , cytokeratin + , vimentin + , and estrogen receptor negative cells.…”

“…LA7 is a well-known rat mammary gland cancer stem cells that can be differentiated to all cell lineages of the mammary gland and is able to induce heterogeneous tumors in non-obese diabetic-SCID mice (22). Tumor induction by transplantation of LA7 cells in animal model, is recently considered as a favored method in cancer research (23). Here, we showed that 16h-SFS solution comprised of some proteins with well-known ability in reduction of the expression of stemness-related genes and in induction of cell death, upon analyzing this solution by LC-ESI-MS/MS.…”

Neuroprotective and anxiolytic potential of green rooibos (Aspalathus linearis) polyphenolic extract

“…Although they work as modulators of plant physiology, they have gained popularity in human health research, as they possess bioactive and pharmacological properties 3,4 which may have substantial benefit in the preventative medicine niche, specifically in terms of non-communicable diseases of lifestyle, 5 but also in the context of cancer. 6 From a nutritional perspective, they behave as non-nutrient bioactive compounds with antioxidant and other modulating properties in a plethora of tissues and organs. 7 The consumption of polyphenolic compounds in our diet has been recently associated with a reduction in the development of certain disorders such as cancer or cardiovascular, metabolic and neurodegenerative diseases.…”