Inhibitory effects of Chinese nutritional herbs in isogenic breast carcinoma cells with modulated estrogen receptor function

Telang, Nitin T.; Guo, Li; Katdare, Meena; Sepkovic, Daniel W.; Bradlow, Leon; Wong, George Y.

doi:10.3892/ol.2016.5197

Cited by 17 publications

(29 citation statements)

References 28 publications

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“…In addition, at this physiological concentration E 2 decreased cell population doubling time, increased saturation density and enhanced AI growth compared with the corresponding control groups. These data are consistent with a recent study, where E 2 concentrations within the physiological range induced progressive increases in viable cell number (14). These results indicate that the method used in the current study produced an optimized E 2 -responsive cell culture model for the Luminal A molecular subtype of breast cancer.…”

Section: Discussionsupporting

confidence: 81%

“…herbs, such as Tabebuia avellandae (TA), CO and LB, on MCF-7 cells (9,10,13,14). The signaling pathways susceptible to extracts from TA, CO and LB include cell proliferation, cellular apoptosis, ER, xenobiotic metabolism and cell cycle progression through the modulated expression of specific genes (9,10,13,14).…”

Section: Discussionmentioning

confidence: 99%

“…The signaling pathways susceptible to extracts from TA, CO and LB include cell proliferation, cellular apoptosis, ER, xenobiotic metabolism and cell cycle progression through the modulated expression of specific genes (9,10,13,14). Additionally, these extracts affect the cellular metabolism of E 2 , as demonstrated through the increased formation of specific anti-proliferative metabolites of E 2 (9)(10)(11)13,14). These results suggest that low-dose treatment with extracts from nutritional herbs is associated with an acceptable toxicity profile for future animal experiments and clinical trials.…”

Section: Discussionmentioning

confidence: 99%

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The nutritional herb Epimedium grandiflorum inhibits the growth in a model for the Luminal A molecular subtype of breast cancer

Telang¹,

Gou²,

Katdare

et al. 2017

Oncology Letters

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Abstract. The Luminal A subtype of breast cancer expresses the estrogen receptor (ER)-α and progesterone receptor (PR), but not the human epidermal growth factor receptor (HER)-2 oncogene. This subtype of breast cancer responds to endocrine therapy involving the use of selective estrogen receptor modulators and/or inhibitors of estrogen biosynthesis. However, these therapeutic agents are frequently associated with long-term systemic toxicity and acquired tumor resistance, emphasizing the need to identify non-toxic alternative treatments for chemo-endocrine therapy responsive breast cancer. The present study utilized the human mammary carcinoma-derived, ER + /PR + /HER-2 -MCF-7 cell line as a model of the Luminal A subtype of breast cancer to examine the growth inhibitory effect of the Chinese nutritional herb Epimedium grandiflorum (EG) and determine the mechanisms underlying this effect. MCF-7 cells maintained in a serum-depleted culture medium retained their ability to grow in response to 17β-estradiol (E 2 ). Treatment of the MCF-7 cells with EG resulted in dose-dependent inhibition of E 2 -promoted growth. Mechanistically, EG inhibited E 2 -promoted cell cycle progression through G 1 stage arrest and modulated the cellular metabolism of E 2 , increasing the formation of the anti-proliferative metabolites 2-hydroxyestrone and estriol. Long-term treatment of MCF-7 cells with EG inhibited E 2 -promoted anchorage independent growth, a surrogate in vitro biomarker of tumorigenesis. In conclusion, the results of the present study demonstrate the growth inhibitory effects of EG on MCF-7 cells and identified clinically relevant mechanistic leads for its anti-tumorigenic efficacy. IntroductionMetastatic breast cancer is one of the leading causes of breast-cancer associated mortality in the United States, and the American Cancer Society (Atlanta, GA, USA) projections for breast cancer incidence and mortality rates estimate 246,660 newly diagnosed cases of invasive breast cancer and 40,450 metastatic breast cancer-associated mortalities in women in 2017 (1). These figures emphasize the requirement for a more precise molecular classification of breast cancer for subtype-specific targeted therapy, in addition to the necessity to identify novel, non-toxic and efficacious modalities as alternatives for cancer prevention and therapy.The global gene expression profiling of breast cancer has led to the identification of molecularly distinct subtypes. Patients with the molecular subtype Luminal A express estrogen receptor-α (ER)-α and progesterone receptor (PR), and they lack the expression of human epidermal growth factor receptor-2 (HER-2). Patients with this subtype respond to endocrine-based targeted therapy, such as selective ER modulators and specific small molecule inhibitors of estrogen biosynthesis (2-4). However, long-term endocrine-based therapy has been associated with adverse systemic toxicity, acquired tumor resistance and the emergence of drug resistant cancer stem cells that compromise therapeutic efficacy and ...

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The nutritional herb Epimedium grandiflorum inhibits the growth in a model for the Luminal A molecular subtype of breast cancer

Telang¹,

Gou²,

Katdare

et al. 2017

Oncology Letters

Self Cite

View full text Add to dashboard Cite

show abstract

“…These agents, due to their inherently minimal toxicity, may provide testable alternatives for limitations of conventional chemo-endocrine and small molecular-targeted therapeutic options. Previously published data on cell culture models for Luminal A, HER-2 enriched and triple negative molecular subtypes of clinical breast cancer have demonstrated that several mechanistically distinct natural phytochemicals and herbal extracts function as cytostatic and pro-apoptotic agents conferring potent growth inhibitory efficacy in these clinically relevant model systems (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”

Section: Growth Inhibitory Efficacy Of Natural Products In a Model Fomentioning

confidence: 99%

“…Anchorage-independent growth is a sensitive and specific in vitro surrogate endpoint for the tumorigenic potential of carcinoma-derived cell lines (12)(13)(14)(15)(19)(20)(21). For this assay, 184-B5 and MDA-MB-231 cell lines at a predetermined cell density were suspended in 0.33% agar and overlaid on a basement layer of 0.6% agar.…”

Section: Mechanistic Biomarkersmentioning

confidence: 99%

Growth inhibitory efficacy of natural products in a model for triple negative molecular subtype of clinical breast cancer

Telang¹

2017

Biomedical Reports

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Abstract. Global gene expression profiling identifies predictive and prognostic biomarkers and rationalizes breast cancer subtype-targeted treatment. The Anthracyclin/Taxol and survival pathway specific small molecular inhibitors, constitute current treatment options. These options are associated with acquired tumor resistance and emergence of drug-resistant cancer stem cells. Dietary supplements and constitutive bioactive phytochemicals with relatively low systemic toxicity may provide testable alternatives for current therapy. Human breast epithelial cell lines 184-B5 (non-tumorigenic triple negative cell type) and MDA-MB-231 (breast carcinoma derived triple negative cell type) were used as the experimental models. Putative cancer chemo-preventive natural products and their constitutive bioactive agents represented the test agents. Anchorage independent growth, cell cycle progression and cell apoptosis quantified the treatment efficacy. Compared to the 184-B5 cells, the MDA-MB-231 cells exhibited anchorage-independent growth indicative of persistent cancer risk. Additionally, the MDA-MB-231 cells exhibited hyper-proliferation, accelerated cell cycle progression and inhibited apoptosis indicative of loss of homeostatic growth control. The test agents inhibited anchorage-independent growth via cytostatic and pro-apoptotic effects. The triple negative carcinoma-derived Doxorubicin-resistant phenotype exhibited cancer stem cell markers, including tumor spheroid formation and expression of CD44, NANOG and c-Myc. These data identify clinically relevant mechanistic leads for the efficacy of natural products in the aggressive therapy-resistant breast cancer subtype and suggests a testable approach for cancer stem cell-targeted therapy.

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Lycium barbarum (goji berry), human breast cancer, and antioxidant profile

Wawruszak

Hałasa

Okła

2021

Cancer

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Inhibitory effects of Chinese nutritional herbs in isogenic breast carcinoma cells with modulated estrogen receptor function

Cited by 17 publications

References 28 publications

The nutritional herb Epimedium grandiflorum inhibits the growth in a model for the Luminal A molecular subtype of breast cancer

The nutritional herb Epimedium grandiflorum inhibits the growth in a model for the Luminal A molecular subtype of breast cancer

Growth inhibitory efficacy of natural products in a model for triple negative molecular subtype of clinical breast cancer

Lycium barbarum (goji berry), human breast cancer, and antioxidant profile

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