scholarly journals Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation

2019 ◽  
Vol 9 (3) ◽  
pp. 445-452 ◽  
Author(s):  
Edy Meiyanto ◽  
Herwandhani Putri ◽  
Yonika Arum Larasati ◽  
Rohmad Yudi Utomo ◽  
Riris Istighfari Jenie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Metastatic Breast Cancer ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Metastatic Breast ◽  
Cell Senescence ◽  
Dependent Manner ◽  
Curcumin Analogue ◽  
4T1 Cells

Purpose: Pentagamavunon-1 (PGV-1) is a curcumin analogue that shows cytotoxic activity in various cancer cells. In this study, we evaluated the effect of PGV-1 on a highly metastatic breast cancer cell line, the 4T1 cells, as an anti-metastatic and anti-proliferative agent. Methods: Cell viability was evaluated using MTT assay; while cell cycle profile, apoptosis incidence, and ROS intracellular level were determined by flow cytometry. Cell senescence was observed under senescence-associated-β-galactosidase (SA-β-gal) staining assay. The expression of matrixmetalloproteinase-9 (MMP-9) was determined using immunoreaction based-ELISA, while other proteins expression were detected using immunoblotting. Results: Curcumin and PGV-1 showed cytotoxic effects on 4T1 cells with IC50 value of 50 and 4 µM, respectively. The cytotoxic activity of PGV-1 was correlated to the induction of G2/M cell cycle arrest and cell senescence. Furthermore, PGV-1 increased the accumulation of intracellular ROS level. We also revealed that PGV-1 bound to several ROS-metabolizing enzymes, including glyoxalase I (GLO1), peroxiredoxin 1 (PRDX1), N-ribosyldihydronicotinamide: quinone reductase 2 (NQO2), aldo-keto reductase family 1 member c1 (AKR1C1). As an antimetastatic agent, PGV-1 showed less inhibitory effect on cell migration compared to curcumin. However, PGV-1 significantly decreased MMP-9 protein expression in a dose-dependent manner suggesting it still potent to inhibit metastatic cells. Conclusion: Overall, our findings suggest that PGV-1 is potential to be developed as an antiproliferative and anti-metastatic agent.

scholarly journals Methanolic Extract of Red Betel Leaves (Piper crocatum Ruiz & Pav) Perform Cytotoxic Effect and Antimigration Activity toward Metastatic Breast Cancer

2018 ◽  
Vol 8 (3) ◽  
pp. 94 ◽  
Author(s):  
Meirizky Zulharini ◽  
Ika Rahmawati Sutejo ◽  
Hilyatul Fadliyah ◽  
Riris Istighfari Jenie
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Methanolic Extract ◽  
Metastatic Breast ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
4T1 Cells

Breast cancer is one type of cancer with a high mortality rate due to its metastatic property. Red betel leaves (Piper crocatum Ruiz dan Pav) has been known as herbal medicine containing biophenolic, such as apigenin and luteolin derivatives which has cytotoxic activity toward cancer cells. This study is intended to explore the inhibitory effect of Piper crocatum leaves methanolic extract (PCM) on cell proliferation and migration by using 4T1 cells as model of metastatic breast cancer. By using MTT assay, PCM performed cytotoxic activity in a dose dependent manner with IC50 value of 120 μg/mL. Wound healing assay revealed that migration inhibitory activity of PCM on 4T1 cells at the concentration of 30 µg/mL. In conclusion, PCM perform cytotoxic effect and antimigration activity toward metastatic breast cancer cells.Keywords : breast cancer cells, Piper crocatum Ruiz & Pav, cytotoxic, cell mgration

Therapeutic Effects of Matrine on Primary and Metastatic Breast Cancer

2010 ◽  
Vol 38 (06) ◽  
pp. 1115-1130 ◽  
Author(s):  
Hali Li ◽  
Gang Tan ◽  
Xian Jiang ◽  
Haiquan Qiao ◽  
Shangha Pan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Metastatic Breast ◽  
Proliferation Index ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Therapeutic Benefits ◽  
4T1 Breast Cancer ◽  
Dose Dependent

Matrine, one of the main components extracted from a traditional Chinese herb, Sophora flavescens Ait, has displayed anti-cancer activity in several types of cancer cells. This study aims to evaluate the therapeutic benefits of matrine on primary and metastatic breast cancer. Matrine inhibited the viability of and induced apoptosis in human MCF-7 and mouse 4T1 breast cancer cells in a dose-dependent manner in vitro as shown by MTT assay, flow cytometry and laser scanning confocal microscopy. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.

Abstract 4307: Molecular basis of cell cycle arrest induced by erufosine in metastatic breast cancer cells

2018 ◽  
Author(s):  
Asim Pervaiz ◽  
Muhammad Shoaib Akhtar ◽  
Saqib Mahmood ◽  
Osheen Sajjad ◽  
Saba Khaliq ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Metastatic Breast Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Molecular Basis ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Cycle Arrest

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 Fingerroot (Boesenbergia pandurata) Extract Inhibits Proliferation and Migration of 4T1 Metastatic Breast Cancer Cells

2020 ◽  
Vol 11 (3) ◽  
pp. 103
Author(s):  
Marsya Yonna Nurrachma ◽  
Gergorius Gena Maran ◽  
Nindya Budiana Putri ◽  
Yuni Fajar Esti ◽  
Adam Hermawan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Metastatic Breast ◽  
Gelatin Zymography ◽  
Breast Cancer Cell Lines ◽  
Cytotoxicity Test ◽  
Intracellular Level ◽  
4T1 Cells

Fingerroot (Boesenbergia pandurata) is an Indonesian herb, with anti-proliferation and anti-migratory effects against several cancer cells. This study aims to investigate the anticancer property of Fingerroot Extract (FE) in combination with doxorubicin (Dox) against 4T1, a metastatic breast cancer cell lines. FE was prepared by 96% ethanol maceration and characterized by thin-layer chromatography analysis. FE was subjected to a cytotoxicity test with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay alone or in combination with 10 nM Dox against 4T1 cells. Cytotoxic effect was then confirmed by measure reactive oxygen species (ROS) intracellular level using 2’,7’-dichloroflourescin diacetate (DCFDA)-staining flow cytometry-based assay. The anti-migratory effect was observed using scratch wound healing assay and gelatin zymography to investigate matrix metalloproteinase (MMP)-9 expression. FE showed a cytotoxic effect with an inhibitory concentration 50 (IC50) value of 25.5±3.9 μg/mL and performed an improved effect in combination with 10 nM Dox. A single treatment of FE decreased ROS intracellular level, while in combination with Dox, FE increased the ROS intracellular level. Further, at 42 h observation, FE and its combination with Dox inhibited the migration of 4T1 cells with % closure of 82.6 and 82.5, respectively, correlates with a significant decrease of MMP-9 expression. Overall, FE performs a cytotoxic activity and anti-migration activity on 4T1 breast cancer cells.Keywords: Boesenbergia pandurata, cytotoxic, ROS, anti-migration, 4T1 

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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