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 Pygenic Acid A (PA) Sensitizes Metastatic Breast Cancer Cells to Anoikis and Inhibits Metastasis In Vivo

2020 ◽  
Vol 21 (22) ◽  
pp. 8444
Author(s):  
Ga-Eun Lim ◽  
Jee Young Sung ◽  
Suyeun Yu ◽  
Younmi Kim ◽  
Jaegal Shim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Breast Cancer Cell Lines ◽  
Syngeneic Mouse Model ◽  
Apoptosis Protein ◽  
4T1 Cells

Metastasis is the main cause of cancer-related deaths. Anoikis is a type of apoptosis caused by cell detachment, and cancer cells become anoikis resistant such that they survive during circulation and can successfully metastasize. Therefore, sensitization of cancer cells to anoikis could prevent metastasis. Here, by screening for anoikis sensitizer using natural compounds, we found that pygenic acid A (PA), a natural compound from Prunella vulgaris, not only induced apoptosis but also sensitized the metastatic triple-negative breast cancer cell lines, MDA-MB-231 cells (human) and 4T1 cells (mouse), to anoikis. Apoptosis protein array and immunoblotting analysis revealed that PA downregulated the pro-survival proteins, including cIAP1, cIAP2, and survivin, leading to cell death of both attached and suspended cells. Interestingly, PA decreased the levels of proteins associated with anoikis resistance, including p21, cyclin D1, p-STAT3, and HO-1. Ectopic expression of active STAT3 attenuated PA-induced anoikis sensitivity. Although PA activated ER stress and autophagy, as determined by increases in the levels of characteristic markers, such as IRE1α, p-elF2α, LC3B I, and LC3B II, PA treatment resulted in p62 accumulation, which could be due to PA-induced defects in autophagy flux. PA also decreased metastatic characteristics, such as cell invasion, migration, wound closure, and 3D growth. Finally, lung metastasis of luciferase-labeled 4T1 cells decreased following PA treatment in a syngeneic mouse model when compared with the control. These data suggest that PA sensitizes metastatic breast cancer cells to anoikis via multiple pathways, such as inhibition of pro-survival pathways and activation of ER stress and autophagy, leading to the inhibition of metastasis. These findings suggest that sensitization to anoikis by PA could be used as a new therapeutic strategy to control the metastasis of breast cancer.

scholarly journals Ethanolic Extract of Hedyotis corymbosa L. Inhibits Migration and MMP-9 Activity on Metastatic Breast Cancer Cells

2018 ◽  
Vol 9 (1) ◽  
pp. 16
Author(s):  
Dhania Novitasari ◽  
Sri Handayani ◽  
Riris Istighfari Jenie
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Gelatin Zymography ◽  
Ethanolic Extract ◽  
Inhibitory Effect ◽  
Anticancer Properties ◽  
Scratch Wound ◽  
4T1 Breast Cancer

Many natural products have been widely explored for their pharmacological activities, including anticancer activity. Hedyotis corymbosa L. is known for its anticancer properties toward several cancer cell lines. The study aims to investigate whether ethanolic extract of Hedyotis corymbosa L. (EEH) performs anticancer properties by inhibiting migration and metastasis on breast cancer cells. Cytotoxic evaluation by using MTT assay was carried out to determine EEH effect on 4T1 breast cancer cells, meanwhile to investigate the treatment of EEH in migration and metastasis inhibitory effect, scratch wound healing assay and gelatin zymography were conducted in this study. The data showed that EEH possessed cytotoxic activity with IC50 value of 400 μg/mL.  Interestingly, migration inhibitory effect was shown up to 42 hours and the activity of MMP-9 was also decreased after the treatment with EEH. According to these findings, we suggest that Hedyotis corymbosa L. promotes another anticancer properties by inhibiting migration and metastasis towards breast cancer cells.Keywords : Hedyotis corymbosa L., cytotoxicity, migration, metastatic, 4T1 breast cancer cells

scholarly journals Oyster Mushroom (Pleurotus ostreatus) Inhibits Migration and Metastasis on 4T1 Breast Cancer Cells

2017 ◽  
Vol 7 (3) ◽  
pp. 99
Author(s):  
Lodyta Nawang Tika ◽  
Layung Sekar Sih Wikanthi ◽  
Shofa Annur ◽  
Retno Murwanti
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Pleurotus Ostreatus ◽  
Breast Cancer Cells ◽  
Anticancer Agent ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Ethanolic Extract ◽  
4T1 Breast Cancer

Metastasis is the main cause of death among brast cancer patient. Pleorotus ostreatus is known as anticancer agent that inhibits angiogenesis. Ethanolic extract of Pleorotus ostreatus (EEP) which contains lovastatin is predicted to inhibit metastatic cancer through inhibition of MMP-2 and MMP-9. The aim of this study was to determined antiproliferative and anti metastatic activity of EEPw (Ethanolic extract of wet Pleorotus ostreatus) and EEPd (Ethanolic extract of dried Pleorotus ostreatus ) in 4T1 metastatic breast cancer cells line. Qualitative analysis of lovastatin was determined by thin layer chromatography (TLC) using dicloromethan and etil acetat as mobile phase and lovastatin standard. Scratch wound healing assay was used to determine migration inhition ability of EEP while MMP-9 and MMP-2 activity were analysed by gelatine zymography. Molecular docking was performed to know the interaction between lovastatin and MMP-2 & MMP-9. The result showed that EEPw and EEPd contain lovastatin which were proved by spray reaction with anisaldehid. Each of EEPw and EPPd had cytotoxic activity with IC50 760 and 400 μg/mL respectively. Both of them inhibited closure for about 50 % on 4T1 metastatic breast cancer cells line compared to control. Either EEPw or EEPd decreased MMP-9 expression level compared to control. Lovastatin had higher affinity to bond with either MMP-2 or MMP-9 than native ligand. Overall, EEP could be developed as anticancer agent which was targeted on MMP-2 and MMP-9.Keywords : Pleurotus ostreatus, 4T1 metastatic cells, MMP-2, MMP-2, antimetastatic

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 Anti-metastatic effect of curcumin analog pentagamaboronon-0-fructose (PGB-0-F) against 4T1 breast cancer cells

2018 ◽  
Vol 23 (2) ◽  
pp. 109
Author(s):  
Yogi Ertanto ◽  
Rohmad Yudi Utomo ◽  
Riris Istighfari Jenie ◽  
Ratna Asmah Susidarti ◽  
Edy Meiyanto
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Metastatic Breast ◽  
Gelatin Zymography ◽  
Metastatic Progression ◽  
Curcumin Analog ◽  
Migration Activity ◽  
4T1 Breast Cancer

Development of a chemotherapeutic agent and boron carrying pharmaceutical based on triple-negative breast cancer is important due to its metastatic progression. Metastases are often more dangerous than the primary tumor and they are responsible for 90% of all cancer deaths. The purpose of this study was to explore the anti-metastatic activities of the PGB-0 complex with fructose (PGB-0-F) against 4T1 breast cancer cells. A scratch wound healing assay was carried out to determine the migration inhibition ability of PGB-0-F, while MMP-9 expression was analysed using gelatin zymography. The testing of anti-migration activity showed that PGB-0-F inhibited in 4T1 cells, whereas the gelatin zymography assay revealed a suppression of MMP-9 expression. PGB-0-F inhibited closure on 4T1 metastatic breast cancer cells line compared with the control. PGB-0-F decreased the MMP-9 expression level compared with the control. Based on these results, PGB-0-F has the potential to be developed as a chemotherapeutic agent, and especially as an anti-metastatic agent.

scholarly journals A Comparative Study on Anticancer Effects of the Alhagi maurorum and Amygdalus haussknechtii Extracts Alone and in Combination with Docetaxel on 4T1 Breast Cancer Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Nayereh Bahamin ◽  
Shahin Ahmadian ◽  
Mahmoud Rafieian-Kopaei ◽  
Gholamreza Mobini ◽  
Mahshid Shafiezadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Pcr Analysis ◽  
Antitumor Effects ◽  
Migration Assay ◽  
Anticancer Effects ◽  
4T1 Cells ◽  
4T1 Breast Cancer

Medicinal plants have long been studied due to their anticancer effects and use of them is commonly increased as a complementary and alternative medicine (CAM therapies) among patients with cancer. In this study, Alhagi maurorum (A.m) and Amygdalus haussknechtii (A.h) extracts were evaluated for their effects on inhibiting the growth of 4T1 breast cancer cells. Based on MTT assay results, the IC50s of A.m and A.h extracts were 57 µg/ml and 85 µg/ml, respectively. Then the cell migration, gene expression, and degree of apoptosis after 48 hours in each treated group with A.m and A.h extracts alone or in combination with docetaxel (DTX) on 4T1 cells were evaluated. A.m had a synergistic behavior with DTX (CI < 1). A.h reduced DTX IC50 but presented CI > 1. Cell migration assay showed that each extract alone or in combination with DTX prevented the migration of 4T1 cells. The Ao/EB staining and flowcytometry results confirmed that, in combination therapy, A.m + DTX and A.h + DTX induced apoptosis close to the level of DTX. Real-time PCR analysis showed that A.m + DTX (IC50 + IC25) downregulated the mRNA expression of HIF-1α and FZD7. A.m + DTX (IC50 + IC10) group decreased the expression of HIF-1α. Moreover, in A.h + DTX (IC50 + IC25) group, β-Catenin and FZD7 were downregulated and upregulated, respectively. Generally, our findings suggest that the combination of A.m and DTX possesses synergistic antitumor effects on 4T1 cells, which may be a valuable choice for CAM therapies. A.h has an acceptable antitumor activity but not in combination with DTX.

Apoptotic Effects of Melittin on 4T1 Breast Cancer Cell Line is associated with Up Regulation of Mfn1 and Drp1 mRNA Expression

2020 ◽  
Vol 20 (7) ◽  
pp. 790-799 ◽  
Author(s):  
Farnaz D. Moghaddam ◽  
Pejman Mortazavi ◽  
Somayeh Hamedi ◽  
Mohammad Nabiuni ◽  
Nasim H. Roodbari
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Hemolytic Activity ◽  
Breast Cancer Cells ◽  
Flow Cytometric Analysis ◽  
Control Group ◽  
Flow Cytometric ◽  
4T1 Cells ◽  
4T1 Breast Cancer ◽  
Apoptotic Effects

Background and Purpose: Melittin, as the main ingredient of honeybee venom, that has shown anticancer properties. The present study aimed at investigating the cytotoxic impacts of melittin on 4T1 breast cancer cells. Methods: Hemolytic activity of different concentrations (0.125, 0.25, 0.5, 1, 2, 4, 8μg/ml) of melittin was assayed and then cytotoxicity of selected concentrations of melittin (2, 4, 8, 16, 32, and 64μg/ml), 2 and 4μg/ml of cisplatin and 0.513, 0.295 and 0.123μg/ml of doxorubicin was evaluated on 4T1 cells using MTT assay. We used Morphological evaluation and flow cytometric analysis was used. Real time PCR was also used to determine mRNA expression of Mfn1 and Drp1 genes. Results: All compounds showed anti-proliferative effects on the tumor cell line with different potencies. Melittin had higher cytotoxicity against 4T1 breast cancer cells (IC50= 32μg/ml-72h) and higher hemolytic activity (HD50= 1μg/ml), as compared to cisplatin and doxorubicin. Mellitin at 16 and 32μg/ml showed apoptotic effects on 4T1 cells according to the flow cytometric analysis. The Real time PCR analysis of Drp1 and Mfn1 expression in cells treated with 16μg/ml of melittin revealed an up-regulation in Drp1 and Mfn1 genes mRNA expression in comparison with control group. Treatment with 32μg/ml of melittin was also associated with a rise in mRNA expression of Drp1 and Mfn1 as compared to the control group. Conclusion: The results of this study showed that melittin has anticancer effects on 4T1 cell lines in a dose and time dependent manner and can be a good candidate for further research on breast cancer treatment.

scholarly journals The migration of metastatic breast cancer cells is regulated by matrix stiffness via YAP signalling

Heliyon ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e06252
Author(s):  
Wei Chen ◽  
Shihyun Park ◽  
Chrishma Patel ◽  
Yuxin Bai ◽  
Karim Henary ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Matrix Stiffness
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