scholarly journals Yuanhuatine from Daphne genkwa selectively induces mitochondrial apoptosis in estrogen receptor α-positive breast cancer cells in vitro

Planta Medica ◽  
2019 ◽  
Vol 85 (16) ◽  
pp. 1275-1286 ◽  
Author(s):  
Ying-Ying Zhang ◽  
Xin-Yue Shang ◽  
Xue-Wen Hou ◽  
Ling-Zhi Li ◽  
Wei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Potential Candidate ◽  
Daphne Genkwa ◽  
Mcf 7 ◽  
Positive Breast Cancer

AbstractBreast cancer is one of the most common cancers diagnosed among women worldwide. Estrogen receptor alpha (ERα) is a transcriptional factor that plays an important role in the development and progression of breast cancer. Yuanhuatine, a natural daphnane-type diterpenoid extracted from Daphne genkwa, was reported to exhibit significant cytotoxicity against breast cancer cells. However, the underlying mechanism is still unclear. In this study, we evaluated the cytotoxicity of yuanhuatine on two breast cancer cell lines that are ERα-positive and -negative. The results show that yuanhuatine inhibits the growth of ERα-positive cells (MCF-7) with much stronger inhibitory activity (IC50 = 0.62 µM) compared with positive control tamoxifen (IC50 = 14.43 µM). However, no obvious cytotoxicity was observed in ERα-negative cells (MDA-MB-231). Subsequent experiment also indicated that yuanhuatine markedly induced mitochondrial dysfunction, leading to apoptosis in MCF-7 cells. Molecular docking studies suggest the potential interactions between yuanhuatine and ERα. Immunofluorescence staining and Western blot analysis indicated that yuanhuatine down-regulated the expression of ERα in MCF-7 cells. MPP, a specific ERα inhibitor, significantly enhanced yuanhuatine-induced mitochondrial dysfunction and apoptosis in MCF-7 cells. On the contrary, the treatment with yuanhuatine causes no apoptosis in MM231 cells. Altogether, in vitro and in silico results suggested that ERα down-regulation was involved in yuanhuatine-induced mitochondrial dysfunction and apoptosis in ERα-positive breast cancer cells. Thus, yuanhuatine could be a potential candidate for treating ERα-positive breast cancer.

Identification of estrogenically synthesized LRP16 as an ERα coactivator and its role in ERα-positive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10676-10676
Author(s):  
W. Han ◽  
Y. Zhao ◽  
Z. Wu ◽  
Y. Mu ◽  
L. Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Northern Blot ◽  
Breast Cancer Cells ◽  
Tumor Diameter ◽  
Er Positive ◽  
Mcf 7 ◽  
Positive Breast Cancer

10676 Background: Aberrant ERα activity is linked to genesis and malignant progression of breast cancer through direct target gene activation or repression. A complex network of coregulatory proteins is largely believed to determine the transcriptional activity of ERα. LRP16 was identified previously to be an estrogen (E2) responsive gene, but its function involving in conferring estrogen signalling pathway is not clear. Methods: Endogenous LRP16 expression in MCF-7 cells was stably suppressed by retrovirus-mediated small interference RNA (siRNA). The effects of LRP16 expression on E2-stimulated growth and invasive ability of MCF-7 cells were determined in vitro and in vivo assays. The effects of LRP16 expression on ERα transactivation were determined by luciferase assays. The interaction of LRP16 and ERα was examined by GST pull-down and coimmunopricipitation (CoIP) assays. Northern blot and Western blot were used to detect the mRNA and protein levels of ER target genes in LRP16-inhibited MCF-7 cells. The LRP16 expression levels in primary breast cancer were detected by Northern blot. Results: Fristly, LRP16 expression was characterized to be dependent on estrogen activities. Then, LRP16 was identified to be an estrogen-independent ERα cofactor in ER-positive breast cancer cells and demonstrate that LRP16 is an essential coactivator to ERα-mediated transactivation in an estrogen-dependent manner. Suppression of LRP16 expression in ER-positive breast cancer cells specifically inhibits the transcription of ER upregulated genes, results in the increase of E-cadherin expression through ER mediation. In vitro and in vivo data demonstrate that suppression of LRP16 inhibits the ability of estrogen-stimulated proliferation and invasiveness of ER-positive breast cancer cells. The pathological and clinical characteristics of human breast cancer includining ER/PR-positiveness, tumor diameter and the involvement of axillary lymphoid nodes were tightly linked with the LRP16 gene expression level. Conclusions: These results establish a mechanistic link between estrogen receptor status, its coactivator LRP16, and progression of ER-positive breast cancers, and may provide a novel antiestrogenic target for the therapy of ER positive breast cancer. No significant financial relationships to disclose.

Suberosin attenuates the proliferation of MCF-7 breast cancer cells in combination with radiotherapy or hyperthermia.

2020 ◽  
Vol 12 ◽  
Author(s):  
Saeedeh Jafari Nodooshan ◽  
Peyman Amini ◽  
Milad Ashrafizadeh ◽  
Saeed Tavakoli ◽  
Tayebeh Aryafar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Study ◽  
Therapeutic Modality ◽  
Potential Candidate ◽  
Therapeutic Efficiency ◽  
Cancer Cell Death ◽  
Mcf 7

Aim: The aim of this study was to determine the proliferation of MCF-7 following irradiation or hyperthermia as alone or pre-treatment with suberosin. Background: Radiotherapy is a major therapeutic modality for the control of breast cancer. However, hyperthermia can be prescribed for relief of pain or enhancing cancer cell death. Some studies have attempted its use as an adjuvant to improve therapeutic efficiency. Suberosin is a cumarin-derived natural agent that has shown anti-inflammatory properties. Objective: In this in vitro study, possible sensitization effect of suberosin in combination with radiation or hyperthermia was evaluated. Method: MCF-7 breast cancer cells were irradiated or received hyperthermia with or without treatment with suberosin. The incidence of apoptosis as well as viability of MCF-7 cells were observed. Furthermore, the expressions of proapoptotic genes such as Bax, Bcl-2, and some caspases were evaluated using real-time PCR. Results: Both radiotherapy or hyperthermia reduced the proliferation of MCF-7 cells. Suberosin amplified the effects of radiotherapy or hyperthermia for induction of pro-apoptotic genes and reducing cell viability. Conclusion: Suberosin has a potent anti-cancer effect when combined with radiotherapy or hyperthermia. It could be a potential candidate for killing breast cancer cells as well as increasing the therapeutic efficiency of radiotherapy or hyperthermia.

Purvalanol A is a strong apoptotic inducer via activating polyamine catabolic pathway in MCF-7 estrogen receptor positive breast cancer cells

2013 ◽  
Vol 41 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Pınar Obakan ◽  
Elif Damla Arısan ◽  
Pelin Özfiliz ◽  
Ajda Çoker-Gürkan ◽  
Narçin Palavan-Ünsal
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Catabolic Pathway ◽  
Estrogen Receptor Positive ◽  
Mcf 7 ◽  
Positive Breast Cancer

Effect of estrogen receptor-positive progenitor cells on a tamoxifen resistance phenotype in breast cancer cells

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1042-1042
Author(s):  
J. Selever ◽  
I. Barone ◽  
M. T. Lewis ◽  
A. Corona-Rodriguez ◽  
A. Tsimelzon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tamoxifen Resistance ◽  
Soft Agar ◽  
Estrogen Receptor Positive ◽  
Mcf 7 ◽  
Positive Breast Cancer

1042 Background: The antiestrogen tamoxifen and aromatase inhibitors are the most frequently prescribed hormonal agents for the treatment of estrogen receptor (ER) α-positive breast cancer. An important question is whether there is a group of hormone resistant, ERα-positive patients who may derive additional benefit from the addition of chemotherapy to endocrine therapy, or who may be candidates for “targeted” biologics. Dicer1 is an RNase III-containing enzyme that processes microRNA precursors into mature microRNA, which have been implicated in breast tumor invasion and metastasis. BCRP1 is a transmembrane transport protein known to efflux a number of chemotherapeutic agents, but also steroid hormones. In the present study, we investigated whether Dicer might affect response to tamoxifen in breast cancer cells, and generated estrogen receptor-positive MCF-7 human breast cancer cells stably overexpressing Dicer1, and they exhibited elevated BCRP1 protein. Methods: We utilized preclinical approaches to study the function of BCRP1 in Dicer-overexpressing breast cancer cells using in vitro growth assays in soft agar, mammosphere formation assays, and in vivo tumor initiation. Results: Microarray analyses of human breast tumors, suggested that Dicer overexpression was associated with tamoxifen resistance. Dicer-overexpressing MCF-7 cells express elevated levels of BCRP1, ALDH, and cErbB2/HER-2 evident by immunoblot analysis. The Dicer1-overexpressing cells formed soft agar colonies in the presence of tamoxifen, however Fumitremorgin C (FTC) or MBLI-97, both BCRP inhibitors, reversed resistance, and sensitized cells to tamoxifen therapy. Preclinical in vivo tumor xenograft experiments confirmed the tamoxifen-resistant phenotype. Mammosphere potential was enhanced in Dicer-overexpressing cells suggesting an enrichment of stem-like breast cancer cells. Conclusions: Our results suggest that Dicer-overexpressing breast cancer cells are a novel preclinical model for an estrogen receptor-positive breast cancer progenitor phenotype and tamoxifen resistance. Based on our data Dicer1 is a potential predictive biomarker in breast cancer, and predicts that clinical BCRP1 inhibition may facilitate tumor sensitization to hormonal therapy. No significant financial relationships to disclose.

Ergosterol (Major Sterol of Baker’s and Brewer’s Yeast Extracts) Inhibits the Growth of Human Breast Cancer Cells in vitro and the Potential Role of its Oxidation Products

2003 ◽  
Vol 73 (1) ◽  
pp. 19-23 ◽  
Author(s):  
M. T. Ravi Subbiah ◽  
W. Abplanalp
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Oxidation Products ◽  
Brewer’S Yeast ◽  
Brewer's Yeast ◽  
Mcf 7

The derivation of chemopreventive agents from dietary sources has been the subject of considerable attention in recent years. Yeast extracts have been used as nutritional supplements for a number of years. In this communication we show that ergosterol (a 28-carbon sterol found in baker’s and brewer’s yeast) can prevent growth of breast cancer cells in vitro in the presence of estradiol-17beta. Estrogen receptor (+) MCF-7 cells appear to be more sensitive to ergosterol than estrogen receptor (–) MDA-231 cells. However, MDA-231 cells were more sensitive to ergosterol in terms of apoptotic effects than MCF-7 cells, indicating that other mechanisms (antiestrogenic activity) may also be operative in estrogen receptor (+) cells. Compared to freshly prepared ergosterol, stored preparations were more potent in inhibiting growth of cancer cells, indicating that oxidation product(s) of ergosterol may be responsible for the noted effects. Further studies on in vivo effects of ergosterol and lipid extracts of yeast in animal models are warranted to determine their potential for use as supplements in humans.

Anticancer Potential of Calli Versus Seedling Extracts Derived from Rosmarinus officinalis and Coleus hybridus

2020 ◽  
Vol 21 (14) ◽  
pp. 1528-1538
Author(s):  
Sarah Albogami ◽  
Hadeer Darwish ◽  
Hala M. Abdelmigid ◽  
Saqer Alotaibi ◽  
Ahmed Nour El-Deen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Transcriptional Profiling ◽  
Significant Inhibition ◽  
Rosmarinus Officinalis ◽  
Crude Extracts ◽  
Incidence And Mortality ◽  
Mcf 7

Background: In Saudi Arabia, the incidence and mortality rates of breast cancer are high. Although current treatments are effective, breast cancer cells develop resistance to these treatments. Numerous studies have demonstrated that active compounds in plant extracts, such as the phenolic compound Rosmarinic Acid (RA), exert anti-cancer effects. Objective: We investigated the anticancer properties of methanolic crude extracts of seedlings and calli of Rosmarinus officinalis and Coleus hybridus, two Lamiaceae species. Methods: MCF-7 human breast cancer cells were treated with methanolic crude extracts obtained from plant calli and seedlings generated in vitro, and cell proliferation was evaluated. Transcriptional profiling of the seedling and callus tissues was also conducted. Results: The mRNA expression levels of RA genes were higher in C. hybridus seedlings than in R. officinalis seedlings, as well as in C. hybridus calli than in R. officinalis calli, except for TAT and C4H. In addition, seedling and callus extracts of both R. officinalis and C. hybridus showed anti-proliferative effects against MCF-7 cells after 24 or 48 h of treatment. Discussion: At a low concentration of 10 μg/mL, C. hybridus calli and seedling extracts showed the most significant anti-proliferative effects after 24 and 48 h of exposure (p < 0.01); controls (doxorubicin) also showed significant inhibition, but lesser than that observed with C. hybridus (p < 0.05). Results with R. officinalis callus and seedling extracts did not significantly differ from those with untreated cells. Conclusion: Methanolic extracts of R. officinalis and C. hybridus are potentially valuable options for breast cancer treatment.

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