Divide and Conquer May Not Be the Optimal Approach to Retain the Desirable Estrogenic Attributes of the Cyclopia Nutraceutical Extract, SM6Met

Mortimer, Morné; Visser, Koch; Beer, Dalene de; Joubert, Elizabeth; Louw, Ann

doi:10.1371/journal.pone.0132950

Cited by 16 publications

(17 citation statements)

References 77 publications

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“…Many phenolic compounds with health promoting benefits have been identified in C. subternata ( De Beer et al, 2012 ; Kokotkiewicz et al, 2012 ). SM6Met is a well-characterized phytoestrogenic extract of C. subternata with a comparable estrogenic potency to commercially available phytoestrogenic nutraceuticals ( Mfenyana et al, 2008 ; Mortimer et al, 2015 ). Previous work from our group have shown that SM6Met antagonizes estrogen-induced BC cell proliferation in vitro ( Visser et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…In addition, a study showed that the presence of lipids in extracts containing phenolic compounds, as found in ID7, helps in the solubilization of these substances in the cells, which may potentiate their activity [17] explaining the relationship of these compounds with the results found. It is not clear yet, whether the observed activity might be due to a synergistic effect of the mixture of compounds in ID7-analogues to observed activity in fighting breast cancer with SM6Met from honey bush te [18].…”

Section: Discussionmentioning

confidence: 99%

“…From the guided fractionation of SM6Met it was observed that it is unlikely that only one compound will be responsible for the estrogenic attributes, but rather that various compounds contribute to the activity of the extract either individually (additive) or inducing a synergistic effect [38]. The idea of intelligent mixtures in the investigation of activity, induced by a mixture of compounds, has become increasingly popular [18]. Thus, it is believed that the five compounds recognized in ID7 can act synergistically providing antitumor and antimetastatic activities found in this work.…”

Section: Discussionmentioning

confidence: 99%

ID7 Isolated from Bauhinia variegata Stem Inhibits Tumor Progression and Metastatic Mechanisms of Triple Negative Breast Cancer in Vivo

Santos¹,

Gomes²,

Oliveira³

et al. 2019

JPP

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Background: The breast cancer has been the most common form of cancer among women. The triple negative subtype represents 20% of all breast cancer cases in the world and is standing out by affecting young women and being aggressive. The main cause of death of patients with cancer is due to metastasis, which can reach the liver and lungs. Objective: The activities of ID7 fraction of the stems of Bauhinia variegata L. on breast cancer, lung metastasis and liver inflammatory process were evaluated. Method: ID7 was characterized by mass-spectrometry. The viability of murine mammary cells (4T1) treated with ID7 was assessed by MTT, trypan blue and fluorescence assay and viability of BT-20, MDA-MB-231 and MCF-7 human breast cancer tumor lines by MTS. The cell migration, invasion using matrigel and adhesion were performed. The expression of cell death proteins was quanitified by western blot and the gelatinases by zimogram. The ID7 activity of the tumor (4T1) and metastatic progession in vivo was evaluated. Results: ID7 reduced the 4T1 and MDA-MB-231viability and increased the late apoptosis, inhibited the 4T1 migration and invasion, increased the 4T1 adhesion and decreased the secreted active gelatinases. ID7 also increased the expression of PARP, caspase-7 and caspase-8, RIP and TNF-R1. In vivo, the ID7 decreased the volume and weight of the tumors and decreased lung metastasis and inflammation in the liver. The characterization showed mainly the presence of oleic acid, myricetin, quercetin and kaempferol in ID7. Conclusion: Thus, it was found that ID7 fraction exhibits selective antitumor and on the mechanisms of breast cancer metastasis activity, preventing lung metastasis and inflammation in the liver. It is suggested that fatty acids and flavonoids are correlated with such activities.

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“…The COS-1 monkey kidney and HEK293 human embryonic kidney cell lines were obtained from the ATCC and cultured as previously described [12,15]. Only mycoplasma-negative cell lines were used in experiments.…”

Section: Methodsmentioning

confidence: 99%

Comparing the androgenic and estrogenic properties of progestins used in contraception and hormone therapy

Toit

Perkins

Hapgood

et al. 2017

Biochemical and Biophysical Research Communications

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Progestins used in endocrine therapies bind to multiple steroid receptors and are associated with several side-effects. It is thus important to understand the relationship between steroid receptor cross-reactivity and the side-effect profile of progestins. In cell lines that express negligible levels of steroid receptors, we report for the first time the binding affinities, potencies and efficacies of selected progestins from different generations determined in parallel. We show that the progestins bind to the androgen receptor (AR) with similar affinities to each other and progesterone, while none bind estrogen receptor (ER)-β, and only norethisterone acetate, levonorgestrel and gestodene bind ERα. Comparative dose-response analysis revealed that progestins from the first three generations display similar androgenic activity to the natural androgen dihydrotestosterone for transactivation, while norethisterone acetate, levonorgestrel and gestodene are ERα agonists. We show for the first time that the anti-androgenic properties of progesterone and drospirenone are similar to the well-known AR antagonist hydroxyflutamide, while nomegestrol acetate is more potent and nestorone less potent than both hydroxyflutamide and progesterone. Moreover, we are the first to report that the older progestins, unlike progesterone and the fourth generation progestins, are efficacious ERα agonists for transrepression, while the selected progestins from the second and third generation are efficacious AR agonists for transrepression. Considering the progestin potencies and their reported free serum concentrations relative to dihydrotestosterone and estradiol, our results suggest that the progestins are likely to exert AR-, but not ERα- or ERβ-mediated effects in vivo.

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Divide and Conquer May Not Be the Optimal Approach to Retain the Desirable Estrogenic Attributes of the Cyclopia Nutraceutical Extract, SM6Met

Cited by 16 publications

References 77 publications

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

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

ID7 Isolated from Bauhinia variegata Stem Inhibits Tumor Progression and Metastatic Mechanisms of Triple Negative Breast Cancer in Vivo

Comparing the androgenic and estrogenic properties of progestins used in contraception and hormone therapy

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