scholarly journals Synergistic Cytotoxicity between Elephantopus scaber and Tamoxifen on MCF-7-Derived Multicellular Tumor Spheroid

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Wan Yong Ho ◽  
Sok Sian Liew ◽  
Swee Keong Yeap ◽  
Noorjahan Banu Alitheen
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Spheroid ◽  
Multicellular Tumor Spheroid ◽  
Synergistic Cytotoxicity ◽  
Estrogen Receptor Positive ◽  
Elephantopus Scaber ◽  
Combinatorial Treatment ◽  
Mcf 7 ◽  
Positive Breast Cancer

Elephantopus scaber Linn, a traditional herb, exhibited anticancer properties, and it was cytotoxic against the monolayer estrogen receptor-positive breast cancer cell line, MCF-7, in the previous study. In order to determine the potential of E. scaber as a complementary medicine for breast cancer, this study aimed to evaluate the synergism between E. scaber and tamoxifen in cytotoxicity using MCF-7 in the form of 3-dimensional multicellular tumor spheroid (MCTS) cultures. MCTS represents a more reliable model for studying drug penetration as compared to monolayer cells due to its greater resemblance to solid tumor. Combination of E. scaber ethanol extract and tamoxifen, which were used in concentrations lower than their respective IC50 values, had successfully induced apoptosis on MCTS in this study. The combinatorial treatment showed >58% increase of lactate dehydrogenase release in cell media, cell cycle arrest at the S phase, and 1.3 fold increase in depolarization of mitochondrial membrane potential. The treated MCTS also experienced DNA fragmentation; this had been quantified by TUNEL-positive assay, which showed >64% increase in DNA damaged cells. Higher externalization of phospatidylserine and distorted and disintegrated spheroids stained by acridine orange/propidium iodide showed that the cell death was mainly due to apoptosis. Further exploration showed that the combinatorial treatment elevated caspases-8 and 9 activities involving both extrinsic and intrinsic pathways of apoptosis. The treatment also upregulated the expression of proapoptotic gene HSP 105 and downregulated the expression of prosurvival genes such as c-Jun, ICAM1, and VEGF. In conclusion, these results suggested that the coupling of E. scaber to low concentration of tamoxifen showed synergism in cytotoxicity and reducing drug resistance in estrogen receptor-positive breast cancer.

scholarly journals Concanavalin-A shows synergistic cytotoxicity with tamoxifen via inducing apoptosis in estrogen receptor-positive breast cancer: In vitro and molecular docking studies

2021 ◽  
Author(s):  
Mohamed Elshal ◽  
Norhan Eid ◽  
Ibrahim El-Sayed ◽  
Wael El-Sayed ◽  
Ahmed Ali Al-Karmalawy
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Molecular Docking ◽  
Concanavalin A ◽  
Combined Treatment ◽  
Con A ◽  
Synergistic Cytotoxicity ◽  
Mcf 7 ◽  
Positive Breast Cancer

Background: Tamoxifen (TAM) is the main treatment of estrogen receptor (ER)-positive breast cancer, however; its adverse effects and development of resistance hinder its use. Concanavalin A (Con A) is a mannose/glucose-binding lectin that has been reported to induce apoptosis in a variety of cell lines. Methods: Therefore, we aimed to elucidate the effects of Con A on TAM-induced cell death in ERα positive cell line (MCF-7) and to identify the potential underlying molecular mechanisms using in silico and in vitro techniques. Results: Our results demonstrated that combined treatment with Con A and TAM reduced the expression of ERα, which showed clear synergistic effects on inhibiting the cell viability of MCF-7 cells. Interestingly, the combined treatment induces G1 phase arrest and reduces cyclin D1 activity while increasing apoptosis and autophagy as indicated by decreasing the expression level of anti-apoptosis gene BCl-2 and increased apoptosis/autophagic gene BNIP3. Molecular docking was conducted to evaluate the binding affinity of Con A towards ERα, and it revealed its potential activity as an ERα antagonist. Our data further indicated that Con A administration increased the drug reduction index of TAM. Conclusion: Overall, our findings suggested that Con A could be used as an adjuvant agent with TAM to improve its effectiveness as an anticancer agent while minimizing its side effects.

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.

scholarly journals Toronto Workshop on Late Recurrence in Estrogen Receptor–Positive Breast Cancer: Part 1: Late Recurrence: Current Understanding, Clinical Considerations

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Ryan J O Dowling ◽  
Kevin Kalinsky ◽  
Daniel F Hayes ◽  
Francois-Clement Bidard ◽  
David W Cescon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
International Workshop ◽  
Recurrence Risk ◽  
Late Recurrence ◽  
Current Understanding ◽  
Breast Cancer Patients ◽  
Related Factors ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Abstract Disease recurrence (locoregional, distant) exerts a significant clinical impact on the survival of estrogen receptor–positive breast cancer patients. Many of these recurrences occur late, more than 5 years after original diagnosis, and represent a major obstacle to the effective treatment of this disease. Indeed, methods to identify patients at risk of late recurrence and therapeutic strategies designed to avert or treat these recurrences are lacking. Therefore, an international workshop was convened in Toronto, Canada, in February 2018 to review the current understanding of late recurrence and to identify critical issues that require future study. In this article, the major issues surrounding late recurrence are defined and current approaches that may be applicable to this challenge are discussed. Specifically, diagnostic tests with potential utility in late-recurrence prediction are described as well as a variety of patient-related factors that may influence recurrence risk. Clinical and therapeutic approaches are also reviewed, with a focus on patient surveillance and the implementation of extended endocrine therapy in the context of late-recurrence prevention. Understanding and treating late recurrence in estrogen receptor–positive breast cancer is a major unmet clinical need. A concerted effort of basic and clinical research is required to confront late recurrence and improve disease management and patient survival.

Late Recurrences After Estrogen Receptor–Positive Breast Cancer

JAMA Oncology ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. 301
Author(s):  
Steven A. Narod ◽  
Vasily Giannakeas ◽  
Victoria Sopik
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer
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