scholarly journals Brazilein in Combination with Cisplatin Inhibit Proliferation and Migration on Highly Metastatic Cancer Cells, 4T1

2017 ◽  
Vol 21 (1) ◽  
pp. 38 ◽  
Author(s):  
Sri Handayani ◽  
Ratna Asmah Susidarti ◽  
Zalinar Udin ◽  
Edy Meiyanto ◽  
Riris Istighfari Jenie
Keyword(s):  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Metastatic Cancer ◽  
Gelatin Zymography ◽  
Inhibitory Effect ◽  
Cycle Progression ◽  
4T1 Cells ◽  
4T1 Breast Cancer ◽  
And Migration ◽  
Induced Apoptosis

Brazilein performs anti­cancer activities on several cancer cells and potentially inhibits metastasis. The aims of this study is to observe the synergistic cytotoxic and migration inhibitory effect of brazilein combined with cisplatin on 4T1 breast cancer cells. Under MTT assay, we found that brazilein revealed cytotoxic effect on 4T1 cells in a dose­dependent manner (IC50=50 ± 0.3 µM). Combination of brazilein and cisplatin showed synergistic effect (CI=0.72). Flowcytometry analysis on the cell cycle progression showed that single treatment of 25 µM brazilein induced G2/M­phase accumulation, 12.5 µM cisplatin induced S­phase accumulation, while combination of brazilein and cisplatin induced S­phase and G2/Mphase accumulation. Combination of brazilein and cisplatin induced apoptosis higher than that of the single treatments. Based on wound healing assay, 12.5 µM brazilein and its combination with 6.25 µM cisplatin inhibited cells migration. Immunoblotting and gelatin zymography analysis showed that combination of brazilein and cisplatin inhibited the expression level of Rac1 and MMP9 proteins. Based on these results, we conclude that brazilein enhanced cytotoxic activity of cisplatin and inhibited migration on 4T1 cells and potentially can be developed as an enhancing cytotoxic and antimetastasis agent.

scholarly journals A Comparison of Antimetastatic Activity between Nerium indicum and Cinnamomum burmannii on 4T1 Cells

2017 ◽  
Vol 8 (2) ◽  
pp. 85 ◽  
Author(s):  
Beni Lestari ◽  
Laeli Muntafiah ◽  
Ziana Walidah ◽  
Riris Istighfari Jenie
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Gelatin Zymography ◽  
Inhibitory Effect ◽  
Scratch Wound ◽  
Metastatic Process ◽  
Cinnamomum Burmannii ◽  
4T1 Cells ◽  
Cinnamon Essential Oil ◽  
4T1 Breast Cancer

Metastatic process becomes a major problem in advanced cancer cases. Natural compounds found in several plants in Indonesia have a potency to be developed as chemoterapeutic agent which are targeted to metastatic process. Jure leaves (Nerium indicum) which contain oleandrin and cinnamaldehyde in cinnamon bark (Cinnamomum burmannii) reported to have cytotoxic activity on several cancer cells, but their activities on metastasic process have never been explored. This research aims to reveal and to compare their anti-metastatic effect toward 4T1 breast cancer cells. The cytotoxicity of jure leaves extract (JLE) and cinnamon essential oil (CEO) was obtained by MTT assay. Metastatic process mainly on cell migration was examined by scratch wound healing assay while MMP-9 expression that described the invassion process was observed by gelatin zymography assay. Molecular interaction between their active compounds and MMP-9 receptor was predicted by molecular docking. The result showed that treatment with JLE and CEO inhibited the growth of 4T1 cells with IC50 value of 125 µg/mL and 2.5 µg/mL, respectively. In addition, JLE performed inhibitory effect of cell migration better than CEO. Meanwhile, both JLE and CEO decreased MMP-9 protein expression. Thus, JLE and CEO have potentials to be developed as an anti-metastatic agent and JLE could be more effective.Key words: Nerium indicum, Cinnamomum burmannii, anti-metastasis, scratch assay, gelatin zimography

Evaluation of GPER agonist G-1 combined with navitoclax in platinum-resistant and -sensitive ovarian cancer cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13563-e13563
Author(s):  
Dennis C. DeSimone ◽  
Trung T. Nguyen ◽  
Eugen Brailiou ◽  
John C. Taylor ◽  
Gabriela Cristina Brailoiu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Parp Cleavage ◽  
Ovarian Cancer Cells ◽  
Cycle Progression ◽  
Platinum Based Chemotherapy ◽  
Induced Apoptosis ◽  
In Cells

e13563 Background: Most ovarian cancer patients are treated with platinum-based chemotherapy but eventually relapse with incurable disease. The G protein-coupled estrogen receptor GPER (GPR30) mediates Ca2+ mobilization in response to estrogen and G-1, a synthetic agonist. Large and sustained Ca2+ responses can lead to mitochondrial Ca2+ overload and apoptosis. Hence, we evaluated whether G-1 could induce apoptosis in cisplatin-sensitive A2780 and isogenic cisplatin–resistant CP70 (14-fold resistant), C30 (70-fold resistant) and C200 (157-fold resistant) human ovarian cancer cells. Bcl-2 and Bcl-xL protect mitochondria from Ca2+overload, and were overexpressed in these cisplatin-resistant cells; thus we also examined combining the Bcl-2 family inhibitor navitoclax with G-1. Methods: Cytoplasmic [Ca2+]c and mitochondrial [Ca2+]m were monitored using microscopy and fluorescent Ca2+ probes. Cell cycle, apoptosis and mitochondrial membrane potential (MMP) were assessed by flow cytometry of propidium iodide, Annexin V and DiIC1(5) -stained cells. The intracellular Ca2+ chelator BAPTA was used to block Ca2+mobilization. Results: Expression of the 53kDa GPER but not the 38 kDa isoform progressively increased with increasing cisplatin resistance. G-1 elicited sustained [Ca2+]c rises that correlated with 53 kDa GPER expression, followed by rises in [Ca2+]m. In all cells, 2.5 μM G-1 blocked cell cycle progression at G2/M, inhibited proliferation, and induced apoptosis (A2780 > C30 > CP70 ≥ C200). G-1 induced p53, caspase-3 and PARP cleavage, and MMP loss. BAPTA prevented G-1’s cell cycle and apoptotic effects in cells showing large Ca2+ mobilization responses but did not in cells with small Ca2+responses. Combining navitoclax with G-1 superadditively decreased cell viability and increased apoptosis. Conclusions: G-1 blocked cell cycle progression and induced apoptosis via a Ca2+-dependent pathway in cells expressing high 53 kDa GPER levels, but via a Ca2+-independent pathway in cells with low 53 kDa GPER expression. G-1 also interacted cooperatively with naviticlax. Therefore, G-1 plus navitoclax shows potential for therapeutic use in platinum-sensitive and -resistant ovarian 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 Artesunate inhibits cell proliferation, migration, and invasion of thyroid cancer by regulating the PI3K/AKT/FKHR pathway

2021 ◽  
Author(s):  
Zhiwei Xu ◽  
Xiaojian Liu ◽  
Daoping Zhuang
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Western Blotting ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
And Migration ◽  
Induced Apoptosis ◽  
Thyroid Cancer Cells

This study characterized the effects of artesunate on thyroid cancer and partially identified its related molecular mechanism. We determined the effect of artesunate on the proliferation of thyroid cancer cells using the MTT assay, cell colony formation experiments, and western blotting, and used flow cytometry to detect the apoptosis of cancer cells. Using a wound-healing assay, Transwell chamber experiments, and western blotting, we determined the effect of artesunate on cancer cell migration. By co-cultivating artesunate with the PI3K agonist, 740Y-P, we also partially identified the molecular mechanism. Artesunate significantly inhibited the growth, proliferation, migration, and invasion of thyroid cancer cells, and promoted the apoptosis of cancer cells. Using co-cultivation with a PI3K agonist, we found that the inhibitory effect of artesunate on cancer cells was mainly due to suppressing the PI3K/AKT/FKHR signaling pathway. By inhibiting the PI3K/AKT/FKHR signaling pathway, artesunate induced apoptosis of thyroid cancer cells and inhibited their proliferation and migration.

scholarly journals Reduced Lamin A/C does Not Facilitate Cancer Cell Transendothelial Migration but Compromises Lung Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2383
Author(s):  
Francesco Roncato ◽  
Ofer Regev ◽  
Sara W. Feigelson ◽  
Sandeep Kumar Yadav ◽  
Lukasz Kaczmarczyk ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Lung Metastasis ◽  
Metastatic Cancer ◽  
Nuclear Lamina ◽  
Transendothelial Migration ◽  
Soft Agar ◽  
Lamin A ◽  
And Migration

The mechanisms by which the nuclear lamina of tumor cells influences tumor growth and migration are highly disputed. Lamin A and its variant lamin C are key lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C in two prototypic metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, and reduced heterochromatin content. Surprisingly, both lamin A/C knockdown cells grew poorly in 3D spheroids within soft agar, and lamin A/C deficient cells derived from spheroids transcribed lower levels of the growth regulator Yap1. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown and their metastasis in lungs was even dramatically reduced. Our results are the first indication that reduced lamin A/C content in distinct types of highly metastatic cancer cells does not elevate their transendothelial migration (TEM) capacity and diapedesis through lung vessels but can compromise lung metastasis at a post extravasation level.

scholarly journals Oncogenic role of ALX3 in cervical cancer cells through KDM2B-mediated histone demethylation of CDC25A

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinhong Qi ◽  
Li Zhou ◽  
Dongqing Li ◽  
Jingyuan Yang ◽  
He Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Cervical Squamous Cell Carcinoma ◽  
Cycle Progression ◽  
Normal Tissues ◽  
Positive Regulator ◽  
Cervical Cancer Cells

Abstract Background Cell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development. This work focused on the function of CDC25A in cervical cancer cell growth and the molecules involved. Methods A GEO dataset GSE63514 comprising data of cervical squamous cell carcinoma (CSCC) tissues was used to screen the aberrantly expressed genes in cervical cancer. The CDC25A expression in cancer and normal tissues was predicted in the GEPIA database and that in CSCC and normal cells was determined by RT-qPCR and western blot assays. Downregulation of CDC25A was introduced in CSCC cells to explore its function in cell growth and the cell cycle progression. The potential regulators of CDC25A activity and the possible involved signaling were explored. Results CDC25A was predicted to be overexpressed in CSCC, and high expression of CDC25A was observed in CSCC cells. Downregulation of CDC25A in ME180 and C33A cells reduced cell proliferation and blocked cell cycle progression, and it increased cell apoptosis. ALX3 was a positive regulator of CDC25A through transcription promotion. It recruited a histone demethylase, lysine demethylase 2B (KDM2B), to the CDC25A promoter, which enhanced CDC25A expression through demethylation of H3k4me3. Overexpression of ALX3 in cells blocked the inhibitory effects of CDC25A silencing. CDC25A was found as a positive regulator of the PI3K/Akt signaling pathway. Conclusion This study suggested that the ALX3 increased CDC25A expression through KDM2B-mediated demethylation of H3K4me3, which induced proliferation and cell cycle progression of cervical cancer cells.

scholarly journals Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jing Du ◽  
Weiwei Chen ◽  
Lijuan Yang ◽  
Juanjuan Dai ◽  
Jiwei Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cycle Progression ◽  
Shh Signaling ◽  
Shh Pathway

Abstract Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression, and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and renders a therapeutic interference option to lung cancer patients with poor prognosis. In this study, we screened and evaluated the specificity of a Chinese herb Scutellariabarbata D. Don extraction (SBE) in repressing SHH signaling pathway to block NSCLC progression. Our study confirmed that aberrant activation of the SHH signal pathway conferred more proliferative and invasive phenotypes to human lung cancer cells. This study revealed that SBE specifically repressed SHH signaling pathway to interfere the SHH-mediated NSCLC progression and metastasis via arresting cell cycle progression. We also found that SBE significantly sensitized lung cancer cells to chemotherapeutic agent DDP via repressing SHH components in vitro and in vivo. Mechanistic investigations indicated that SBE transcriptionally and specifically downregulated SMO and consequently attenuated the activities of GLI1 and its downstream targets in SHH signaling pathway, which interacted with cell cycle checkpoint enzymes to arrest cell cycle progression and lead to cellular growth inhibition and migration blockade. Collectively, our results suggest SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway.

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.

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