scholarly journals Pitaya Extracts Induce Growth Inhibition and Proapoptotic Effects on Human Cell Lines of Breast Cancer via Downregulation of Estrogen Receptor Gene Expression

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Deborah de Almeida Bauer Guimarães ◽  
Danielle dos Santos Bonfim De Castro ◽  
Felipe Leite de Oliveira ◽  
Eduardo Matos Nogueira ◽  
Marco Antônio Mota da Silva ◽  
...  

Breast cancer is one of the most prevalent cancers in the world and is also the leading cause of cancer death in women. The use of bioactive compounds of functional foods contributes to reduce the risk of chronic diseases, such as cancer and vascular disorders. In this study, we evaluated the antioxidant potential and the influence of pitaya extract (PE) on cell viability, colony formation, cell cycle, apoptosis, and expression of BRCA1, BRCA2, PRAB, and Erα in breast cancer cell lines (MCF-7 and MDA-MB-435). PE showed high antioxidant activity and high values of anthocyanins (74.65 ± 2.18). We observed a selective decrease in cell proliferation caused by PE in MCF-7 (ER+) cell line. Cell cycle analysis revealed that PE induced an increase in G0/G1 phase followed by a decrease in G2/M phase. Also, PE induced apoptosis in MCF-7 (ER+) cell line and suppressed BRCA1, BRCA2, PRAB, and Erα gene expression. Finally, we also demonstrate that no effect was observed with MDA-MB-435 cells (ER−) after PE treatment. Taken together, the present study suggests that pitaya may have a protective effect against breast cancer.

Phytomedicine ◽  
2015 ◽  
Vol 22 (1) ◽  
pp. 153-157 ◽  
Author(s):  
M.S. Camargo ◽  
M.T. Oliveira ◽  
M.M. Santoni ◽  
F.A. Resende ◽  
A.P. Oliveira-Höhne ◽  
...  

2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14637-e14637
Author(s):  
L. Ko ◽  
J. Allalunis-Turner

e14637 Background: DCA is a generic, orally available, small molecule metabolic modulator that has an established history in the treatment of mitochondrial diseases and lactic acidosis. DCA inhibits pyruvate dehydrogenase kinase (PDK), an inhibitor of pyruvate dehydrogenase, a key enzyme in glucose metabolism. DCA preferentially shifts glucose metabolism in cancer cells from glycolysis to glucose oxidation, reversing the unique aerobic glycolysis found in solid tumors. DCA induced apoptosis in cancer cells as evidenced by the efflux of cytochrome c and apoptosis-inducing factor from the mitochondria. Recent studies suggested apoptosis induction by DCA in glioblastoma, endometrial, prostate, and non-small cell lung cancers. In this study we attempt to establish a link between DCA and apoptosis in breast cancer cell lines. Methods: Six breast cancer cell lines were investigated (BT474, MCF-7, MDA-MB231, MDA- MB468, SKBR3, T47D). Quantitative real-time polymerase chain reaction (RT-PCR) was performed using Taqman probes to identify increased DNA templates of PDK isoforms 1–4, using DCA concentrations from 0 to 20mM. Western blots were performed to identify increased expression of PDK isoforms and correlate findings with Taqman. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium) assays were performed to measure decreased mitochondrial activity and cytotoxicity. Flow cytometry using annexin V and propidium iodide was performed to measure apoptosis and cell death. Results: RT-PCR showed increased DNA expression of all PDK isoforms in MDA-MB231 cells after DCA treatment. The effect was most pronounced at 10mM concentration. 10mM of DCA also increased DNA expression of all PDK isoforms in MCF-7 cells, and PDK1 in T47D cells. MTS assays showed increased cell kill and decreased mitochondrial activity in all six cell lines, with IC50 ranging between 20mM and 30 mM. Flow cytometry showed increased apoptosis induced by DCA at IC50 for BT474 and MCF-7 cell lines. Conclusions: Apoptosis appears to play a role in the mechanism of DCA in breast cancer, with increased PDK isoform expressions, cytotoxicity and decreased mitochondrial activity. Data from flow cytometry suggested DCA-induced apoptosis in two cell lines. No significant financial relationships to disclose.


2018 ◽  
Vol Volume 11 ◽  
pp. 2409-2417 ◽  
Author(s):  
Longfei Yang ◽  
Huanran Liu ◽  
Min Long ◽  
Xi Wang ◽  
Fang Lin ◽  
...  

2017 ◽  
Vol 46 (4) ◽  
pp. 575-581 ◽  
Author(s):  
Siti P.M. Bohari ◽  
Hamidreza Aboulkheyr E.S. ◽  
Nur S. Johan ◽  
Nursyuhada F. Zainudin

2020 ◽  
Author(s):  
Julia Samson ◽  
Kellie Dean

Abstract Background: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010. Methods: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile. Results: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in receptor tyrosine kinase pathways and DNA replication/cell cycle programs. Conclusions: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.


2021 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  

Abstract Background: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA (miRNA) expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated.Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex assay, flow cytometry and transwell inserts were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively.Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential regulated downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a known mediator on invasion and metastasis, and the tumor suppressor gene RUNX3.Conclusions: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have a specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers


2016 ◽  
Vol 2 (1) ◽  
pp. 34
Author(s):  
Tarwadi . ◽  
Churiyah . ◽  
Olivia Bunga Pongtuluran ◽  
Fifit Juniarti ◽  
Fery Azis Wijaya

Sambiloto (Andrographis paniculata) banyak digunakan untuk mengobati berbagai penyakit di Indonesia dan negara-negara Asia lainnya. Dalam studi ini, ekstrak metanol dan etanol sambiloto yang diperoleh dari B2PTO Tawangmangu telah diuji terhadap sel lini kanker payudara T47D dan MCF-7 dan sel lini normal fibroblast HFL-1 menggunakan reaksi enzimatik 3-(4,5-dimethylthiazoyl-2-yl) 2,5-diphenyltetrazoliumbromide (MTT). Uji in vitro terhadap sel lini normal fibroblast HFL-1 menunjukkan bahwa 50 ppm ekstrak metanol sambiloto tidak menghambat pertumbuhan sel. Tetapi, ekstrak metanol dan etanolnya menghasilkan IC50 yang relatif rendah pada sel lini kanker payudara, yaitu 111 ppm dan 122 ppm pada sel lini MCF-7 dan 70 ppm dan 197 ppm pada sel lini T47D. Selain itu, campuran ekstrak sambiloto yang mengandung 25% ekstrak Thyponium divaricatum dan Anredera cordifolia memberikan daya hambat pertumbuhan pada sel kanker payudara MCF-7 yang lebih besar, dengan nilai IC50 masing-masing adalah 68 ppm dan 34 ppm. Kesimpulannya, total ekstrak metanol atau etanol sambiloto yang diperoleh dari Tawangmangu memiliki potensi sebagai sumber senyawa anti-kanker serta perlu kajian lebih lanjut.Kata kunci: Ekstrak Andrographis paniculata, MTT, sel lini normal, sel lini kanker, aktivitas anti kanker ABSTRACTSambiloto (Andrographis paniculata) is widely used as medicine to treat various diseases in Indonesia and other Asian countries. In this study, methanolic and ethanolic extracts of sambiloto collected from B2PTO Tawangmangu have been tested againts breast cancer cell lines of T47D and MCF-7 and normal fibroblast cell line of HFL-1 using enzymatic reaction of 3-(4,5-dimethylthiazoyl-2-yl) 2,5-diphenyltetrazoliumbromide (MTT). In vitro assay performed on normal fibroblast of HFL-1 cell line showed that 50 ppm of methanolic extract of sambiloto did not inhibit cell growth. However, methanolic and ethanolic extracts of sambiloto gave relatively low of IC50 on breast cancer cell lines which were 111 ppm and 122 ppm on the MCF-7 cell lines and 70 ppm and 197 ppm on the T47D cell lines, respectively. In addition, the mixture of sambiloto extract containing 25% of Thyponium divaricatum and Anredera cordifolia extracts confered greater growth inhibition on breast cancer cell line of MCF-7, where IC50 values were 68 ppm and 34 ppm, respectively. In conclusion, the total methanolic or ethanolic extract of sambiloto collected from Tawangmangu has potency as a source of anti-cancer compounds and needs further study.Key words: Andrographis paniculata extract, MTT, normal cell line, cancer cell lines, anti-cancer activity


2019 ◽  
Vol 19 (15) ◽  
pp. 1874-1886
Author(s):  
Maria Schröder ◽  
Shazie Yusein-Myashkova ◽  
Maria Petrova ◽  
Georgi Dobrikov ◽  
Mariana Kamenova-Nacheva ◽  
...  

Background: Drug resistance is a major cause of cancer treatment failure. Most cancer therapies involve multiple agents, to overcome it. Compounds that exhibit strong anti-tumor effect without damaging normal cells are more and more in the focus of research. Chemotherapeutic drugs, combining different moieties and functional groups in one molecule, can modulate different regulatory pathways in the cell and thus reach the higher efficacy than the agents, which affect only one cellular process. Methods: We tested the effect of recently synthesized ferrocene-containing camphor sulfonamide DK-164 on two breast cancer and one breast non-cancer cell lines. The cytotoxic effects were evaluated using the standard MTT-dye reduction and clonogenic assays. The apoptotic or autophagic effects were evaluated by Annexin v binding or LC3 puncta formation assays respectively. Cell cycle arrest was determined using flow cytometry. Western blot and immunofluorescent analyses were used to estimate the localization and cellular distribution of key regulatory factors NFκB and p53. Results: Compound DK-164 has well pronounced cytotoxicity greater to cancer cells (MDA-MB-231 and MCF-7) compared to non-cancerous (MCF-10A). IC50 of the substance caused a cell cycle arrest in G1 phase and induced apoptosis up to 24 hours in both tumor cells, although being more pronounced in MCF-7, a functional p53 cell line. Treatment with IC50 concentration of the compound provoked autophagy in both tumor lines but is better pronounced in the more aggressive cancer line (MDA-MB-231). Conclusion: The tested compound DK-164 showed promising properties as a potential therapeutic agent.


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