Cytotoxicity Activity of Ethanol Extract of Andaliman Fruits (Zanthoxylum acanthopodium DC.) towards 4T1 Breast Cancer Cells

2019 ◽  
Vol 2 (2) ◽  
pp. 31-35
Author(s):  
Rosidah Rosidah ◽  
Poppy Anjelisa Zaitun Hasibuan ◽  
Ginda Haro ◽  
Denny Satria
Keyword(s):  
Breast Cancer ◽  
Natural Products ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Ethanol Extract ◽  
Chemotherapeutic Agents ◽  
Cytotoxicity Activity ◽  
4T1 Cells ◽  
4T1 Breast Cancer

Breast cancer is one of the world's leading cause of death in women. Due to the resistance of chemotherapeutic agents, there is a continuous need to search of natural products with anticancer activity.  The use of natural products  is expected to increase the effectiveness  and decrease side effect. The purpose of this study was to investigate the anticancer activity of ethanol extract of andaliman fruits (EEAF) towards 4T1 cells. Extracts were prepared by maceration using solvent ethanol 96%. 4T1 cells were grown in culture medium DMEM then given by EEAF and doxorubicin. Cytotoxic test in vitro was done by MTT method [3-(4,5-dimetiltiazol-2-il) -2.5 difeniltetrazolium bromide] which is then analyzed using SPSS 21. The results from this study showed that the cytotoxic results (IC50) after treatment with EEAF and doxorubicin were 54.48 ± 0.22 µg/mL dan 0.80 ± 0.02 µg/mL.Based on the result above, we conclude that EEAF has cytotoxic activity towards 4T1 cancer cells. Key words: andaliman fruits, Zanthoxylum acanthopodium DC., ethanol extract, breast cancer, 4T1 cell line.

scholarly journals Antitumor and Anti-Metastatic Effects of Citral-Loaded Nanostructured Lipid Carrier in 4T1-Induced Breast Cancer Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2670 ◽  
Author(s):  
Noraini Nordin ◽  
Swee Keong Yeap ◽  
Heshu Sulaiman Rahman ◽  
Nur Rizi Zamberi ◽  
Nurul Elyani Mohamad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
In Vitro Cytotoxicity ◽  
Nanostructured Lipid Carrier ◽  
Antitumor Effects ◽  
4T1 Cells ◽  
4T1 Breast Cancer

Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than citral alone. Results from the in vivo study indicated that both NLC-Citral and citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated citral. This study suggests that NLC is a potential and effective delivery system for citral to target triple-negative breast cancer.

scholarly journals N-Dihydrogalactochitosan Potentiates the Radiosensitivity of Liver Metastatic Tumor Cells Originated from Murine Breast Tumors

2019 ◽  
Vol 20 (22) ◽  
pp. 5581
Author(s):  
Chung-Yih Wang ◽  
Chun-Yuan Chang ◽  
Chun-Yu Wang ◽  
Kaili Liu ◽  
Chia-Yun Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Synergistic Effects ◽  
Metastatic Breast ◽  
Treatment Modalities ◽  
X Rays ◽  
Dna Breaks ◽  
4T1 Cells ◽  
4T1 Breast Cancer

Radiation is a widely used therapeutic method for treating breast cancer. N-dihydrogalactochitosan (GC), a biocompatible immunostimulant, is known to enhance the effects of various treatment modalities in different tumor types. However, whether GC can enhance the radiosensitivity of cancer cells remains to be explored. In this study, triple-negative murine 4T1 breast cancer cells transduced with multi-reporter genes were implanted in immunocompetent Balb/C mice to track, dissect, and identify liver-metastatic 4T1 cells. These cells expressed cancer stem cell (CSC) -related characteristics, including the ability to form spheroids, the expression of the CD44 marker, and the increase of protein stability. We then ex vivo investigated the potential effect of GC on the radiosensitivity of the liver-metastatic 4T1 breast cancer cells and compared the results to those of parental 4T1 cells subjected to the same treatment. The cells were irradiated with increased doses of X-rays with or without GC treatment. Colony formation assays were then performed to determine the survival fractions and radiosensitivity of these cells. We found that GC preferably increased the radiosensitivity of liver-metastatic 4T1 breast cancer cells rather than that of the parental cells. Additionally, the single-cell DNA electrophoresis assay (SCDEA) and γ-H2AX foci assay were performed to assess the level of double-stranded DNA breaks (DSBs). Compared to the parental cells, DNA damage was significantly increased in liver-metastatic 4T1 cells after they were treated with GC plus radiation. Further studies on apoptosis showed that this combination treatment increased the sub-G1 population of cells, but not caspase-3 cleavage, in liver-metastatic breast cancer cells. Taken together, the current data suggest that the synergistic effects of GC and irradiation might be used to enhance the efficacy of radiotherapy in treating metastatic tumors.

scholarly journals A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 362 ◽  
Author(s):  
Fairouz Sioud ◽  
Souheila Amor ◽  
Imène ben Toumia ◽  
Aida Lahmar ◽  
Virginie Aires ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Protective Action ◽  
Dependent Manner ◽  
4T1 Breast Cancer ◽  
Induced Apoptosis ◽  
Cellular Modifications

Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin.

scholarly journals A Combination of an Antimitotic and a Bromodomain 4 Inhibitor Synergistically Inhibits the Metastatic MDA-MB-231 Breast Cancer Cell Line

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Thandi Mqoco ◽  
André Stander ◽  
Anna-Mart Engelbrecht ◽  
Anna M Joubert
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer

2008 ◽  
Vol 27 (2) ◽  
pp. 143-147 ◽  
Author(s):  
Lorne J Brandes
Keyword(s):  
Breast Cancer ◽  
Dna Synthesis ◽  
Cancer Cells ◽  
Multiple Drug Resistance ◽  
Metastatic Breast ◽  
Chemotherapeutic Agents ◽  
Multiple Drug ◽  
Glycoprotein P ◽  
Hormetic Effect

N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene) is a novel anti-histaminic and chemopotentiating agent that has a hormetic effect on DNA synthesis in MCF (Michigan Cancer Foundation)-7 human breast cancer cells in vitro and stimulates the growth of experimental tumors in rodents. In a prospectively randomized phase three trial (NCIC MA.19), 152 patients who were co-administered DPPE and doxorubicin survived 50% longer ( P < 0.03) than 153 patients who were administered the same dose and schedule of doxorubicin alone. At clinically relevant in vitro concentrations that do not inhibit the P-glycoprotein (P-gp) pump, DPPE selectively sensitizes the cancer cells that express the multiple drug resistance phenotype, making them more susceptible to the cytotoxic effects of chemotherapeutic agents, including anthracyclines and taxanes. Based on its previously demonstrated interaction with histamine at CYP3A4, a P450 that metabolizes arachidonic acid, and its induction of high levels of prostacyclin in the gut of rodents, modulation by DPPE of the intracellular concentration of arachidonate products, such as hydroxyeicosatetraeinoic acids, implicated in increased cancer cell proliferation and metastasis, is postulated.

scholarly journals In Vitro Cytotoxic Study and Detection of Apoptosis on Breast Cancer Cell lines MDA-MB 231 after Exposed to Azadirachta Indica A. Juss (neem) Extract

2013 ◽  
Vol 2 (2) ◽  
pp. 80 ◽  
Author(s):  
Dessy Arisanty
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Azadirachta Indica ◽  
Cell Apoptosis ◽  
Ethanol Extract ◽  
Tunel Assay ◽  
Neem Extract

AbstrakSuatu senyawa obat dapat menjadi kemoterapi kanker adalah dengan cara menskrining terlebih dahulu tumbuhan obat yang berpotensi sebagai obat antikanker. Salah satunya adalah tanaman obat daun nimba (Azadirachta indica L.Juss) yang terbukti secara significant menyebabkan apoptosis pada beberapa jenis sel line kanker. Dalam penelitian ini, ekstrak ethanol dari A. indica dipelajari untuk melihat efeknya pada pertumbuhan sel kanker payudara manusia jenis MDA-MB-231 dengan menggunakan tes untuk proliferasi yaitu MTT assai dan untuk mengetahui perubahan morphologi dari apoptosis selnya dengan menggunakan TUNEL assay Ekstrak daun nimba (A. indica) dapat menurunkan keberadaan jumlah sel kanker dengan cara menghambat perkembangan daripada sel tersebut dan menginduksi proses apoptosis pada sel kanker tersebut. Hasil pemeriksaan MTT assai didapatkan nilai IC50 nya adalah 55 ug / mL. Kematian MDA-MB231 sel yang disebabkan oleh ekstrak daun nimba (A.indica) ditemukan melalui mekanisme apoptosis yang secara morfologinya menunjukan ciri ciri dari kematian secara apoptosis seperti kondensasi dari nucleus, membrane nukleus yang melebur dan akhirnya terjadinya fragmentasi dari DNA. Analisis struktur dalaman sel juga mengungkapkan karakteristik apoptosis yaitu marginasi dari kromosom yang disertai dengan fragmentasi DNA dan selanjutnya akan terbentuk badan apoptotik pada sel kanker yang diinkubasi dengan ekstrak tersebut. Pada penelitian ini juga dijumpai peningkatan jumlah sel apoptosis dari hari 1 sampai hari 3 inkubasi oleh ekstrak nimba. Ekstrak ethanol A.indica mungkin mengandung senyawa bioaktif(s) yang menyebabkan kanker payudara MDA-MNB 231 mengalami kematian sel secara apoptosis. Penelitian lebih lanjut masih diperlukan untuk mengetahui mekanisme tumbuhan ini membunuh sel kanker MDA-MB 231.Kata kunci: Studi In vitro, Azadirachta indica, apoptosis, TUNEL assayAbstractA screening is conducted on plants that have potential as anticancer is a promising way for discovering novel chemotherapeutic compound. A medicinal plant neem leaf (Azadirachta indica L.Juss) intake has been shown to induce significant levels of apoptosis in various cancer cells. In this present study, ethanol extract of Azadirachta indica was studied for its effects on growth in MDA-MB 231 human breast cancer cells using assays for proliferation (MTT assay) and mechanisme of cell apoptosis using TUNEL assay. Neem leaf extract decreased cell viability, inhibited cell proliferation, and induced cell apoptosis. Result of MTT assay was 55 μg/mL of neem remarkably reduced cell viability of MDA-MB 231 cells. MDA-MB231 cell death elicited by the extract was found to be apoptotic in nature based the indication of nucleus condensation, shrinkage of nucleus membrane and also DNA fragmentation which are a hallmark of apoptosis. In addition, ultrastructural analysis also revealed apoptotic characteristics which are the presence of chromatin margination and apoptotic bodies in the extract-treated cells. There was an increase in the number of apoptotic cells from day 1 to day 3 post incubation with neem extract. Thus, the results from this study strongly suggest that the ethanol extract of A.indica may contain bioactive compound(s) that caused breast carcinoma, MDA-MNB 231 cell death by apoptosis. It’s needed to do advance research to know more deeply the mechanism this plant on breast cancer cell line MDA-MB.Keywords:In vitro study, Azadirachta indica, apoptosis, TUNEL assay

scholarly journals Crosstalk between Cancer Cells and Fibroblasts for the Production of Monocyte Chemoattractant Protein-1 in the Murine 4T1 Breast Cancer

2021 ◽  
Vol 43 (3) ◽  
pp. 1726-1740
Author(s):  
Mayu Imamura ◽  
Tiantian Li ◽  
Chunning Li ◽  
Masayoshi Fujisawa ◽  
Naofumi Mukaida ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Pdgf Receptor ◽  
Breast Cancer Patients ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
4T1 Cells ◽  
4T1 Breast Cancer

The chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) is shown to promote the progression of breast cancer. We previously identified cancer cell-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) as a potential regulator of MCP-1 production in the murine 4T1 breast cancer, but it played a minimum role in overall MCP-1 production. Here, we evaluated the crosstalk between 4T1 cells and fibroblasts. When fibroblasts were co-cultured with 4T1 cells or stimulated with the culture supernatants of 4T1 cells (4T1-sup), MCP-1 production by fibroblasts markedly increased. 4T1 cells expressed mRNA for platelet-derived growth factor (PDGF)-a, b and c, and the PDGF receptor inhibitor crenolanib almost completely inhibited 4T1-sup-induced MCP-1 production by fibroblasts. However, PDGF receptor antagonists failed to reduce MCP-1 production in tumor-bearing mice. Histologically, 4T1 tumors contained a small number of αSMA-positive fibroblasts, and Mcp-1 mRNA was mainly associated with macrophages, especially those surrounding necrotic lesions on day 14, by in situ hybridization. Thus, although cancer cells have the capacity to crosstalk with fibroblasts via PDGFs, this crosstalk does not play a major role in MCP-1 production or cancer progression in this model. Unraveling complex crosstalk between cancer cells and stromal cells will help us identify new targets to help treat breast cancer patients.

Botanical Therapeutics (Part II): Antimicrobial and In Vitro Anticancer Activity against MCF7 Human Breast Cancer Cells of Chamomile, Parsley and Celery Alcoholic Extracts

2020 ◽  
Vol 21 (2) ◽  
pp. 187-200
Author(s):  
Corina Danciu ◽  
Oana Cioanca ◽  
Claudia Watz Farcaș ◽  
Monica Hancianu ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Phytochemical Composition ◽  
Antimicrobial Potential

Background: This study was designed as a continuation of a complex investigation about the phytochemical composition and biological activity of chamomile, parsley, and celery extracts against A375 human melanoma and dendritic cells. Objective: The main aim was the evaluation of the antimicrobial potential of selected extracts as well as the in vitro anticancer activity against MCF7 human breast cancer cells. Methods: In order to complete the picture regarding the phytochemical composition, molecular fingerprint was sketched out by the help of FTIR spectroscopy. The activity of two enzymes (acetylcholinesterase and butyrylcholinesterase) after incubation with the three extracts was spectrophotometrically assessed. The antimicrobial potential was evaluated by disk diffusion method. The in vitro anticancer potential against MCF7 human breast cancer cells was appraised by MTT, LDH, wound healing, cell cycle, DAPI, Annexin-V-PI assays. Results: The results showed variations between the investigated extracts in terms of inhibitory activity against enzymes, such as acetyl- and butyrilcholinesterase. Chamomile and parsley extracts were active only against tested Gram-positive cocci, while all tested extracts displayed antifungal effects. Among the screened samples at the highest tested concentration, namely 60μg/mL, parsley was the most active extract in terms of reducing the viability of MCF7 - human breast adenocarcinoma cell line and inducing the release of lactate dehydrogenase. On the other hand, chamomile and celery extracts manifested potent anti-migratory effects. Furthermore, celery extract was the most active in terms of total apoptotic events, while chamomile extract induced the highest necrosis rate. Conclusion: The screened samples containing phytochemicals belonging in majority to the class of flavonoids and polyphenols can represent candidates for antimicrobial and anticancer agents.

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