Modulation of MicroRNAs by Euphorbia Microsciadia Boiss in MDA-MB-231 Cell Line: New Possibilities in Breast Cancer Therapy

Background: A large number of Euphorbia species have been evaluated for anticancer effects; however, their anticancer mechanisms have not been established up to now. Objective: : The present study aimed to evaluate the effects of Euphorbia microsciadia (E. microsciadia) Boiss on the modulation of micro (mi) RNAs in MDA-MB-231 cell line. Methods: As the first step, the inhibitory concentration of hydroalcoholic extract of E. microsciadia on MDA-MB-231 cells was examined using the MTT assay, bypassing 24 and 48h from seeding. The real-time quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was also utilized to determine Let-7, miR-15, miR-16, miR-29, miR-151, miR-155, miR-21, miR-146b, miR-181b, miR-221, miR-222, miR-21, and miR-146b expressions in MDA-MB-231 cells, by passing 24 and 48h from treating with the extract of E. microsciadia. Results: The results reveal the cytotoxic effects of E. microsciadia on MDA-MB-231 cell line in a dose-dependent manner. The half maximal Inhibitory Concentrations (IC50) were also equal to 275 and 240μg/ml for E. microsciadia, by passing 24 and 48h from the treatment, respectively. Furthermore, it was confirmed that, E. microsciadia had augmented the expression levels of Let-7, miR-15, miR-16, miR-29, and miR-34a, which lead to an increase in apoptosis. Conclusion: E. microsciadia could modulate some miRNAs involved in cell cycle arrest and apoptosis in MDA-MB-231 cell line. Accordingly, targeting miRNAs by E. microsciadia can open some newer avenues for breast cancer therapy.

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The effect of Euphorbia szovitsii Fisch. & C.A.Mey extract on the viability and the proliferation of MDA-MB-231 cell line

Bioscience Reports ◽

10.1042/bsr20181538 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 3

Author(s):

Majid Asadi-Samani ◽

Mahmoud Rafieian-Kopaei ◽

Zahra Lorigooini ◽

Hedayatollah Shirzad

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Cell Line ◽

Cultured Cells ◽

Cancer Cell Line ◽

Annexin V ◽

Underlying Mechanism ◽

Dependent Manner ◽

Cycle Arrest

Abstract Some medicinal herbs and compounds are known to target cancer cells, but the success of them as anticancer compounds depends to a large extent on their ability to activate pathways that kill cancer cells by arresting cell cycle and inducing apoptosis. The aim of the present study was to determine the anticancer effects of Euphorbia szovitsii Fisch. & C.A.Mey. on the breast cancer cells to reveal the underlying mechanism of its anti-breast cancer properties. In this experimental study, triple negative breast cancer cell line (MDA-MB-231) was cultivated in RPMI-1640 medium. Hydroalcoholic extract (70:30) of aerial parts of the plant was prepared. The cultured cells were treated with different concentrations (0–1000 μg/ml) of E. szovitsii extract for 24 and 48 h. Toxicity of the extract on MDA-MB-231 cells was examined using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) test. The Annexin V–FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to differentiate different phases of the cell cycle in the cells. Data were analyzed by GraphPad Prism and SPSS software. After 24 and 48 h, the IC50 values were respectively 76.78 (95% CI = 60.75–97.05; R = 0.8588) and 59.71 (95% CI = 46.25–77.09; R = 0.8543) μg/ml for E. szovitsii. The extract exhibited antiproliferative effects against MDA-MB-231 cells in a dose-dependent manner. Annexin V-FITC/PI assay confirmed that the extract was able to induce apoptosis in MDA-MB-231 cells. Moreover, treatment with the extract resulted in cell cycle arrest at G1 phase. Therefore, E. szovitsii could induce apoptosis and cycle arrest in the MDA-MB-231 cell line. It might be a good resource of natural products for producing anti-breast cancer drugs.

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Anticancer activity, phytochemical screening and acute toxicity evaluation of an aqueous extract of Aristolochia longa L.

International Journal of Pharmaceutical and Phytopharmacological Research ◽

10.24896/eijppr.2016614 ◽

2017 ◽

Vol 6 (1) ◽

pp. 20 ◽

Cited By ~ 3

Author(s):

Bachir Benarba ◽

Atanasio Pandiella ◽

Almahy Elmallah

Keyword(s):

Breast Cancer ◽

Acute Toxicity ◽

Cell Lines ◽

Aqueous Extract ◽

Flavonoid Glycosides ◽

Dependent Manner ◽

Oral Toxicity ◽

Cytotoxic Effects ◽

Tlc Analysis ◽

Dose Dependent

Aristolochia longa (Aristolochiaceae) is widely used in traditional medicine. The present study was carried out to investigate the cytotoxic activity and the acute toxicity of an aqueous extract of A. longa roots. Also, the phytochemical composition of the extract was evaluated. The cytotoxic effects of the aqueous extract in triple negative breast cancer MDA-MB-231 and HBL-100 cell lines was evaluated by MTT assay. A. longa roots were screened for the presence of phytochemical constituents using the standard qualitative phytochemical procedures. The acute oral toxicity (5000 mg/kg limited dose test) was evaluated. Our results showed that both cells were inhibited in a dose-dependent manner by A. longa aqueous extract. The IC50 of A. longa aqueous extract was estimated after 72h treatment at 40μg/ml and 97μg/ml in HBL100 and MDA-MB-231 cell lines, respectively. A. longa aqueous extract at a concentration of 500μg/ml suppressed effectively the cell growth of HBL100 and MDA-MB-231 cells. TLC analysis revealed the presence of flavonols, flavones and/or flavonoid glycosides as major compounds in the extract. Results of the acute toxicity study suggest the non-toxicity of the A. longa aqueous extract to the liver. Interestingly, the renal function was not affected by the extract administration at 5000mg/kg. A. longa aqueous extract could be toxicologically safe when administered orally in rats in a single dose. A. longa could be considered as a promising and safe source for developing novel therapeutics against breast cancer. Keywords: Aristolochia longa, breast cancer, phytochemical, acute toxicity, TLC.

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Casein Kinase CK2 Inhibition Results in Tumor Suppression.

Blood ◽

10.1182/blood.v114.22.5052.5052 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5052-5052

Author(s):

Hanan Mohammad ◽

Daniel j Lindner ◽

Michael Kalafatis

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Protein Kinase ◽

Cancer Therapy ◽

Hela Cell ◽

Cell Line ◽

Cell Lines ◽

Cancer Tissue ◽

Cycle Arrest ◽

Hela Cell Lines

Abstract Abstract 5052 Protein Kinase II (CK2) is a pleiotropic, and ubiquitous serine/threonine kinase taht utilizes both ATP and GTP as phosphate donors. Protein kinase CK2 mostly exists as a tetramer composed of two catalytic subunits α and α‘, which exists in heterogeneous or homogenous nature, and two regulatory β subunits. CK2 is a key regulator of signaling pathways involved in cell cycle, proliferation and apoptosis. It is consistently overexpressed in cancer tissue and capable of shuttling between cellular compartments but mainly localized in the nuclear matrix of cancer cells. CK2 is highly involved in apoptosis suppression, oncogene activation and tumorigenesis. It is also considered a bad prognostic marker in cancer tissue and is suggested to be a promising target for cancer therapy. In this study, we examined the effect, of a specific protein kinase inhibitor, and ATP competitor, 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT), on the growth of various cancer types. We have reported DMAT as a potent cancer therapy. In vitro analysis of the viability of hematologic neoplasms and solid tumors, including human lymphoma U937, hormone dependent breast cancer MCF7, hormone independent breast cancer MDA-MB231 and MDA-MB468, and human cervical cancer HeLa cell lines, revealed marked reduction of cellular viability upon treatment with different DMAT concentration at varying time periods. Lymphoma cell line U937 showed an IC50 between 6 -12 μM. A sharp decrease in cancer cells growth was specifically observed following DMAT treatment of cervical carcinoma HeLa cell line with IC50 between 0.2-0.3 μM. Each of the breast cancer cell lines showed IC50 of 6, 10, and 20 μM DMAT for MDA-MB468, MCF7 and MDA-MB231 respectively. The more cancer cell lines we screen, the more evidence we have to suggest DMAT as a potential anti-cancer therapy. However, the specific mechanism of action of DMAT-inhibited-CK2 pathway in cancer ablation is not clear yet. Using Propidium-Iodide staining in conjunction with flow cytometry techniques, we analyzed and compared cell cycles of treated U937, MCF-7, MDA-MB231, MDA-MB468, and HeLa cell lines. Our data indicate that DMAT induces cell cycle arrest in HeLa cell line at G0/G1 phase. No effect on cell cycle was observed for all other cell lines tested. However, all cell lines underwent apoptosis following treatment with DMAT. Thus far our results suggest that DMAT can induce cell cycle arrest, apoptosis and maybe necrosis or multiple processes at the same time. We suggest that the mechanism of DMAT in cancer inhibition could be of multiple actions which further validate this molecule as a potent cancer therapy that could be suitable for clinical investigation. Disclosures No relevant conflicts of interest to declare.

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Cytotoxic Effects of Artemisia annua L. and Pure Artemisinin on the D-17 Canine Osteosarcoma Cell Line

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1615758 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Gloria Isani ◽

Martina Bertocchi ◽

Giulia Andreani ◽

Giovanna Farruggia ◽

Concettina Cappadone ◽

...

Keyword(s):

Cell Line ◽

Artemisia Annua ◽

Iron Concentration ◽

Osteosarcoma Cell Line ◽

Osteosarcoma Cell ◽

Dependent Manner ◽

Intracellular Iron ◽

Cytotoxic Effects ◽

Hydroalcoholic Extract ◽

Canine Osteosarcoma

Artemisia annua has been used for centuries in Traditional Chinese Medicine. Although used as an antimalarial drug, its active compound artemisinin and the semisynthetic derivatives have also been investigated for their anticancer properties, with interesting and promising results. The aims of this research were to evaluate (i) the cytotoxicity and the antiproliferative effect of pure artemisinin and a hydroalcoholic extract obtained from A. annua on the D-17 canine osteosarcoma cell line and (ii) the intracellular iron concentration and its correlation with the cytotoxic effects. Both artemisinin and hydroalcoholic extract induced a cytotoxic effect in a dose-dependent manner. Pure artemisinin caused an increase of cells in the S phase, whereas the hydroalcoholic extract induced an evident increase in the G2/M phase. A significant decrease of iron concentration was measured in D-17 cells treated with pure artemisinin and hydroalcoholic extract compared to untreated cells. In conclusion, although preliminary, the data obtained in this study are indicative of a more potent cytotoxic activity of the hydroalcoholic extract than pure artemisinin, indicating a possible synergistic effect of the phytocomplex and a mechanism of action involving iron and possibly ferroptosis. Considering the similarities between human and canine osteosarcomas, progress in deepening knowledge and improving therapeutic protocols will probably be relevant for both species, in a model of reciprocal translational medicine.

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Scaphium affine Ethanol Extract Induces Anoikis by Regulating the EGFR/Akt Pathway in HCT116 Colorectal Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.621346 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hye Won Kawk ◽

Gun-He Nam ◽

Myeong Jin Kim ◽

Sang-Yong Kim ◽

Young-Min Kim

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Cell Line ◽

Hct116 Cell ◽

Akt Pathway ◽

Dependent Manner ◽

Anticancer Effects ◽

Colorectal Cancer Cells ◽

Dose Dependent

Scaphium affine ethanol extracts (SAE) is a species that has been shown to contain various physiological effects; however, its anticancer effects have yet to be revealed. We qualitatively evaluated β-sitosterol in SAE through high-performance liquid chromatography (HPLC). The cytotoxicity in HCT116 and HT29 colorectal cancer cells and CCD841 normal colon cells was confirmed through WST-1 assays. Selective cytotoxicity was observed in colorectal cancer cells, with greater cytotoxicity demonstrated in the HCT116 cell line. As such, the HCT116 colorectal cell line was selected for subsequent experiments. After HCT116 cells were treated with SAE, it was confirmed that the apoptosis rate was increased in a SAE dose-dependent manner through Annexin V assay. SAE further showed dose-dependent suppression of invasion through invasion assays. Anoikis induction through the EGFR/Akt pathway in HCT116 colorectal cancer cells was confirmed by Western blotting. The tumor suppressive effects of SAE was assessed in vivo using a xenograft model of human HCT116 colorectal cancer cells. As a result, we confirmed that SAE decreased tumor size in a dose-dependent manner and that p-EGFR and cleaved-caspase 3 in tumors were also regulated in a dose-dependent manner. This study showed that SAE, by containing β-sitosterol with proven anticancer effects, induces anoikis through the EGFR/Akt pathway in HCT116 colorectal cancer cells both in vitro and in vivo.

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In vivo activation of mitochondrial pathway and cell cycle arrest through silymarin loaded iron nanoparticles as proficient nanocomplex system for triple negative breast cancer therapy

Annals of Oncology ◽

10.1093/annonc/mdx655.020 ◽

2017 ◽

Vol 28 ◽

pp. x21

Author(s):

M. Paulpandi

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Therapy ◽

Triple Negative Breast Cancer ◽

Iron Nanoparticles ◽

Triple Negative ◽

Mitochondrial Pathway ◽

Breast Cancer Therapy ◽

Cycle Arrest

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Tumor Targeting by Conditioned Medium Derived From Human Amniotic Membrane: New Insight in Breast Cancer Therapy

Technology in Cancer Research & Treatment ◽

10.1177/15330338211036318 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110363

Author(s):

Ameneh Jafari ◽

Mostafa Rezaei-Tavirani ◽

Hassan Niknejad ◽

Hakimeh Zali

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Cancer Cells ◽

Conditioned Medium ◽

Amniotic Membrane ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Human Amniotic Membrane ◽

Dependent Manner ◽

Breast Cancer Therapy

Objectives: Traditional breast cancer treatments have challenges including inefficiency, multidrug resistance, severe side effects, and targeting non-specifically. The development of alternative treatment strategies has attracted a great deal of interest. Using the amniotic membrane has become a promising and convenient new approach for cancer therapy. This study aimed to evaluate the anti-cancer ability of conditioned medium extracted from the human amniotic membrane (hAM-CM) on breast cancer cells. Methods: Conditioned medium was collected after 48 h incubation of hAM in epithelial up manner. MTT, cell cycle, apoptosis, colony formation, and sphere assays were used to determine the impact of hAM-CM on breast cancer cell lines. The effects of hAM-CM on the migration and invasion of breast cancer cells were determined using scratch wound healing and transwell assays, respectively. Results: Based on the results, cell viability was significantly decreased by hAM-CM in a dose-dependent manner. The hAM-CM remarkably induced apoptosis and necrosis of cancer cells. Moreover, cell migration and invasion potential of cancer cells decreased after the hAM-CM treatment. Further, both the number of colonies and their morphologies were affected by the treatment. In the treated group, a significant decrease in the number of colonies along with an obvious change in their morphologies from holoclone shape to a dominant paracolone structure was observed. Conclusion: Our results indicate that the conditioned medium derived from the human amniotic membrane able to inhibit proliferation and metastasis of tumor cells and can be considered a natural and valuable candidate for breast cancer therapy.

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