scholarly journals ST09, A Novel Curcumin Derivative, Blocks Cell Migration by Inhibiting Matrix Metalloproteases in Breast Cancer Cells and Inhibits Tumor Progression in EAC Mouse Tumor Models

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4499
Author(s):  
Snehal Nirgude ◽  
Raghunandan Mahadeva ◽  
Jinsha Koroth ◽  
Sujeet Kumar ◽  
Kothanahally S. Sharath Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Death ◽  
Cell Migration ◽  
Drug Toxicity ◽  
Mouse Tumor ◽  
Curcumin Derivative

Purpose: Curcumin is known for its anticancer and migrastatic activity in various cancers, including breast cancer. Newer curcumin derivatives are being explored to overcome limitations of curcumin like low bioavailability, stability, and side effects due to its higher dose. In this study, the synthesis of ST09, a novel curcumin derivative, and its antiproliferative, cytotoxic, and migrastatic properties have been explored both in vitro and in vivo. Methods: After ST09 synthesis, anticancer activity was studied by performing standard cytotoxicity assays namely, lactate dehydrogenase (LDH) release assay, 3-(4, 5-dimethylthiazol-2-yl)-2–5-diphenyletrazolium bromide (MTT), and trypan blue exclusion assay. Annexin-FITC, cell cycle analysis using flow cytometry, and Western blotting were performed to elucidate cell death mechanisms. The effect on the inhibition of cell migration was studied by transwell migration assay. An EAC (Ehrlich Ascites carcinoma) induced mouse tumor model was used to study the effect of ST09 on tumor regression. Drug toxicity was measured using aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and flow-cytometry based lymphocyte count. Histological analysis was performed for assessment of any tissue injury post ST09 treatment. Results: ST09 shows an approximate 100-fold higher potency than curcumin, its parent compound, on breast tumor cell lines MCF-7 and MDA-MB231. ST09 arrests the cell cycle in a cell type-specific manner and induces an intrinsic apoptotic pathway both in vitro and in vivo. ST09 inhibits migration by downregulating matrix metalloprotease 1,2 (MMP1,2) and Vimentin. In vivo, ST09 administration led to decreased tumor volume in a mouse allograft model by boosting immunity with no significant drug toxicity. Conclusion: ST09 exhibits antiproliferative and cytotoxic activity at nanomolar concentrations. It induces cell death by activation of the intrinsic pathway of apoptosis both in vitro and in vivo. It also inhibits migration and invasion. This study provides evidence that ST09 can potentially be developed as a novel antitumor drug candidate for highly metastatic and aggressive breast cancer.

A Novel Camptothecin Derivative 3j Inhibits Nsclc Proliferation Via Induction of Cell Cycle Arrest By Topo I-Mediated DNA Damage

2019 ◽  
Vol 19 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Yang Liu ◽  
Jingyin Zhang ◽  
Shuyun Feng ◽  
Tingli Zhao ◽  
Zhengzheng Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Dna Damage ◽  
Cyclin D ◽  
Dna Relaxation ◽  
Cycle Arrest ◽  
H460 Cell ◽  
H1975 Cell

Objective: The aim of this study is to investigate the inhibitory effect of camptothecin derivative 3j on Non-Small Cell Lung Cancer (NSCLCs) cells and the potential anti-tumor mechanisms. Background: Camptothecin compounds are considered as the third largest natural drugs which are widely investigated in the world and they suffered restriction because of serious toxicity, such as hemorrhagic cystitis and bone marrow suppression. Methods: Using cell proliferation assay and S180 tumor mice model, a series of 20(S)-O-substituted benzoyl 7- ethylcamptothecin compounds were screened and evaluated the antitumor activities in vitro and in vivo. Camptothecin derivative 3j was selected for further study using flow cytometry in NSCLCs cells. Cell cycle related protein cyclin A2, CDK2, cyclin D and cyclin E were detected by Western Blot. Then, computer molecular docking was used to confirm the interaction between 3j and Topo I. Also, DNA relaxation assay and alkaline comet assay were used to investigate the mechanism of 3j on DNA damage. Results: Our results demonstrated that camptothecin derivative 3j showed a greater antitumor effect in eleven 20(S)-O-substituted benzoyl 7-ethylcamptothecin compounds in vitro and in vivo. The IC50 of 3j was 1.54± 0.41 µM lower than irinotecan with an IC50 of 13.86±0.80 µM in NCI-H460 cell, which was reduced by 8 fold. In NCI-H1975 cell, the IC50 of 3j was 1.87±0.23 µM lower than irinotecan (IC50±SD, 5.35±0.38 µM), dropped by 1.8 fold. Flow cytometry analysis revealed that 3j induced significant accumulation in a dose-dependent manner. After 24h of 3j (10 µM) treatment, the percentage of NCI-H460 cell in S-phase significantly increased (to 93.54 ± 4.4%) compared with control cells (31.67 ± 3.4%). Similarly, the percentage of NCI-H1975 cell in Sphase significantly increased (to 83.99 ± 2.4%) compared with control cells (34.45 ± 3.9%) after treatment with 10µM of 3j. Moreover, increased levels of cyclin A2, CDK2, and decreased levels of cyclin D, cyclin E further confirmed that cell cycle arrest was induced by 3j. Furthermore, molecular docking studies suggested that 3j interacted with Topo I-DNA and DNA-relaxation assay simultaneously confirmed that 3j suppressed the activity of Topo I. Research on the mechanism showed that 3j exhibited anti-tumour activity via activating the DNA damage response pathway and suppressing the repair pathway in NSCLC cells. Conclusion: Novel camptothecin derivative 3j has been demonstrated as a promising antitumor agent and remains to be assessed in further studies.

scholarly journals Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2204
Author(s):  
Meng-Die Yang ◽  
Yang Sun ◽  
Wen-Jun Zhou ◽  
Xiao-Zheng Xie ◽  
Qian-Mei Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cell Viability ◽  
Synergistic Effects ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

scholarly journals Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

2021 ◽  
Author(s):  
Xu Han ◽  
Xiujuan Qu ◽  
Beixing Liu ◽  
Yizhe Wang ◽  
Yang Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Molecular Docking ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Drug ◽  
Specific Gene ◽  
In Vivo Models

Abstract Background: Triple negative breast cancer (TNBC) is a tumor characterized by high recurrence and mortality, but without effective targeted therapy. It is urgent to explore new treatment strategy to improve the efficacy of TNBC therapy. Methods: Transcriptomic profiling datasets of TNBC were used for screening TNBC specific gene sets. Drug prediction was performed in Connectivity map (CMap) database. Molecular docking method was used for analyzing drug targets. In vitro and in vivo models of TNBC were constructed to examine the drug efficacy. Results: We screened out Mibefradil, a T-type Ca2+ channel blocker, might be a potential therapeutic drug for TNBC by transcriptomics and bioinformatics analysis, and verified that Mibefradil could inhibit the proliferation of TNBC cells by inducing apoptosis and cell cycle arrest. Furthermore, by network pharmacology and molecular docking analysis, AURKA was predicted as the most possible drug target of Mibefradil. Finally, it was proved that Mibefradil treatment could induce apoptosis by decreasing protein expression and phosphorylation level of AURKA in vitro and in vivo. Conclusions: Mibefradil played anti-cancer role in TNBC cells by targeting to AURKA to induce cell cycle and apoptosis. Our results repurposed Mibefradil as a potential targeted drug of TNBC and provided a fundamental research for a novel strategy TNBC treatment.

scholarly journals A short ERK5 isoform modulates nucleocytoplasmic shuttling of active ERK5 and associates with poor survival in breast cancer

2021 ◽  
Author(s):  
Mariska Miranda ◽  
Jodi M. Saunus ◽  
Seçkin Akgül ◽  
Mahdi Moradi Marjaneh ◽  
Jamie R. Kutasovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Splice Variants ◽  
Clinicopathological Features ◽  
Full Length ◽  
Nucleocytoplasmic Shuttling ◽  
Poor Survival ◽  
Mesenchymal Transition

AbstractBackgroundThe nucleocytoplasmic shuttling of ERK5 has gained recent attention as a regulator of its diverse roles in cancer progression but the exact mechanisms for this shuttling are still under investigation.MethodsUsing in vitro, in vivo and in silico studies, we investigated the roles of shorter ERK5 isoforms in regulating the nucleocytoplasmic shuttling of active phosphorylated-ERK5 (pERK5). Retrospective cohorts of primary and metastatic breast cancer cases were used to evaluate the association of the subcellular localization of pERK5 with clinicopathological features.ResultsExtranuclear localization of pERK5 was observed during cell migration in vitro and at the invasive fronts of metastatic tumors in vivo. The nuclear and extranuclear cell fractions contained different isoforms of pERK5, which are encoded by splice variants expressed in breast and other cancers in the TCGA data. One isoform, isoform-3, lacks the C-terminal transcriptional domain and the nuclear localization signal. The co-expression of isoform-3 and full-length ERK5 associated with high epithelial-to-mesenchymal transition (EMT) and poor patient survival. Experimentally, expressing isoform-3 with full-length ERK5 in breast cancer cells increased cell migration, drove EMT and led to tamoxifen resistance. In breast cancer patient samples, pERK5 showed variable subcellular localizations where its extranuclear localization associated with aggressive clinicopathological features, metastasis, and poor survival.ConclusionOur studies support a model of ERK5 nucleocytoplasmic shuttling driven by splice variants in an interplay between mesenchymal and epithelial states during metastasis. Using ERK5 as a biomarker and a therapeutic target should account for its splicing and context-dependent biological functions.Graphical AbstractERK5 isoform-3 expression deploys active ERK5 (pERK5) outside the nucleus to facilitate EMT and cell migration. In cells dominantly expressing isoform-1, pERK5 shuttles to the nucleus to drive cell expansion.

scholarly journals A Novel Panel of Rabbit Monoclonal Antibodies and Their Diverse Applications Including Inhibition of Clostridium perfringens Epsilon Toxin Oligomerization

Antibodies ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 37 ◽  
Author(s):  
Jennifer Linden ◽  
Kiel Telesford ◽  
Samantha Shetty ◽  
Paige Winokour ◽  
Sylvia Haigh ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Death ◽  
Monoclonal Antibodies ◽  
Western Blot ◽  
Clostridium Perfringens ◽  
Specificity And Sensitivity ◽  
Epsilon Toxin ◽  
Blocking Antibodies

The pore-forming epsilon toxin (ETX) produced by Clostridium perfringens is among the most lethal bacterial toxins known. Sensitive antibody-based reagents are needed to detect toxin, distinguish mechanisms of cell death, and prevent ETX toxicity. Using B-cell immuno-panning and cloning techniques, seven ETX-specific monoclonal antibodies were generated from immunized rabbits. ETX specificity and sensitivity were evaluated via western blot, ELISA, immunocytochemistry (ICC), and flow cytometry. ETX-neutralizing function was evaluated both in vitro and in vivo. All antibodies recognized both purified ETX and epsilon protoxin via western blot with two capable of detecting the ETX-oligomer complex. Four antibodies detected ETX via ELISA and three detected ETX bound to cells via ICC or flow cytometry. Several antibodies prevented ETX-induced cell death by either preventing ETX binding or by blocking ETX oligomerization. Antibodies that blocked ETX oligomerization inhibited ETX endocytosis and cellular vacuolation. Importantly, one of the oligomerization-blocking antibodies was able to protect against ETX-induced death post-ETX exposure in vitro and in vivo. Here we describe the production of a panel of rabbit monoclonal anti-ETX antibodies and their use in various biological assays. Antibodies possessing differential specificity to ETX in particular conformations will aid in the mechanistic studies of ETX cytotoxicity, while those with ETX-neutralizing function may be useful in preventing ETX-mediated mortality.

scholarly journals Anticancer Activity of Cynomorium coccineum

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 354 ◽  
Author(s):  
Mouna Sdiri ◽  
Xiangmin Li ◽  
William Du ◽  
Safia El-Bok ◽  
Yi-Zhen Xie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression

The extensive applications of Cynomorium species and their rich bioactive secondary metabolites have inspired many pharmacological investigations. Previous research has been conducted to examine the biological activities and numerous interesting pharmaceutical activities have been reported. However, the antitumor activities of these species are unclear. To understand the potential anticancer activity, we screened Cynomorium coccineum and Cynomorium songaricum using three different extracts of each species. In this study, the selected extracts were evaluated for their ability to decrease survival rates of five different cancer cell lines. We compared the cytotoxicity of the three different extracts to the anticancer drug vinblastine and one of the most well-known medicinal mushrooms Amaurederma rude. We found that the water and alcohol extracts of C. coccineum at the very low concentrations possessed very high capacity in decreasing the cancer cells viability with a potential inhibition of tumorigenesis. Based on these primitive data, we subsequently tested the ethanol and the water extracts of C. coccineum, respectively in in vitro and in vivo assays. Cell cycle progression and induction of programmed cell death were investigated at both biological and molecular levels to understand the mechanism of the antitumor inhibitory action of the C. coccineum. The in vitro experiments showed that the treated cancer cells formed fewer and smaller colonies than the untreated cells. Cell cycle progression was inhibited, and the ethanol extract of C. coccineum at a low concentration induced accumulation of cells in the G1 phase. We also found that the C. coccineum’s extracts suppressed viability of two murine cancer cell lines. In the in vivo experiments, we injected mice with murine cancer cell line B16, followed by peritoneal injection of the water extract. The treatment prolonged mouse survival significantly. The tumors grew at a slower rate than the control. Down-regulation of c-myc expression appeared to be associated with these effects. Further investigation showed that treatment with C. coccineum induced the overexpression of the tumor suppressor Foxo3 and other molecules involved in inducing autophagy. These results showed that the C. coccineum extract exerts its antiproliferative activity through the induction of cell death pathway. Thus, the Cynomorium plants appear to be a promising source of new antineoplastic compounds.

scholarly journals P06.01 Delta24-ACT oncolytic adenovirus as a therapeutic approach for DIPG

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii36-iii36
Author(s):  
V Laspidea ◽  
M Puigdelloses ◽  
M García-Moure ◽  
I Iñigo-Marco ◽  
J Gallego ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Death ◽  
Cell Lines ◽  
In Vivo Studies ◽  
Immunogenic Cell Death ◽  
Murine Models ◽  
Antitumoral Effect ◽  
Infected Cells

Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor, being the leading cause of pediatric death caused by cancer. We previously showed that administration of the oncolytic virus Delta-24-RGD to DIPG murine models was safe and led to an increase in the median survival of these animals. However, not all the animals responded, underscoring the need to improve this therapy. In order to increase the antitumoral effect of the virus, we have engineered Delta-24-RGD with the costimulatory ligand 4-1BBL (Delta24-ACT). 4-1BB is a costimulatory receptor that promotes the survival and expansion of activated T cells, and the generation and maintenance of memory CD8+ T cells. In this project, we evaluated the oncolytic effect of Delta24-ACT and the antitumor immune response in DIPG murine models. MATERIALS AND METHODS We use the NP53 and XFM murine DIPG cell lines. Flow cytometry was used to assess cell infectivity and ligand expression. We analyzed viral replication using a method based in hexon detection, and viral cytotoxic effect using the MTS assay. For immunogenic cell death analysis, we measured ATP secretion by a luminometric assay and calreticulin location by flow cytometry and immunofluorescence. For in vivo studies, cells and virus were injected in the pons of the mice, using the screw-guided system. RESULTS In vitro, Delta24-ACT was able to infect and induce cell death in a dose-dependent manner in murine DIPG cell lines. In addition, Delta24-ACT was able to replicate in these tumor cells and to express viral proteins. Moreover, infected cells expressed 41BBL in their membranes. Delta24-ACT could induce immunogenic cell death due to an increased secretion of ATP and calreticulin translocation to the membrane of infected cells (in no-infected cells it located in the ER), DAMPs that can trigger the immune response activation. In vivo, Delta24-ACT demonstrated to be safe in all the tested doses and was able to induce a significant increase in the median survival of the treated animals. Moreover, long-term survivors display immunological memory. CONCLUSIONS Delta24-ACT treatment led to antitumoral effect in DIPG murine cell lines in vitro. Of significance, we have demonstrated that in vivo administration of Delta24-ACT is safe and results in an enhanced antitumor effect. Future in vivo studies will explore the underlying immune mechanism of the virus.

Tumor Hypoxia Promotes Dissemination and Tumor Colonization In Waldenström Macroglobulinemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3011-3011 ◽  
Author(s):  
Barbara Muz ◽  
Feda Azab ◽  
Pilar De La Puente ◽  
Ravi Vij ◽  
Abdel Kareem Azab
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Tumor Hypoxia ◽  
Hypoxic Conditions ◽  
Bm Niche ◽  
E Cadherin

Abstract Introduction Waldenström Macroglobulinemia (WM) is a rare, low-grade B-cell lymphoma characterized by lymphoplasmacytic cells spread widely in the bone marrow (BM) and overproduction of monoclonal immunoglobulins M (IgM). Previous studies showed that tumor hypoxia develops in the BM of other hematologic malignancies and promotes dissemination. In this study, we tested the effect of hypoxia on cell proliferation, cell cycle and apoptosis; on egress and homing of WM cells from and into the BM; and on recovery and tumor colonization in the new BM niche. Methods We characterized the effect of tumor progression on generation of hypoxic conditions in the BM in vivo, by injecting BCWM1-mCherry cells to SCID mice, letting them grow for two weeks, analyzing the hypoxic state of the WM cells in the BM using pimonidazole, and testing the number of circulating cells. Moreover, we tested the effect of hypoxia on the homing of WM cells to the BM by injecting normoxic and hypoxic cells to mice and monitoring the number of the circulating WM cells in the blood at different time points by flow cytometry. Cancer cell colonization was assessed 1 and 3 days post IV injection of normoxic and hypoxic cells to mice; mononuclear cells were isolated from the BM, fixed, permeabilized and stained with antibodies for p-Rb and cyclin-E. The percentile of WM cells in the BM and the expression of cell cycle proteins were analyzed by flow cytometry. BCWM1 cells were exposed to normoxia (21% O2) or hypoxia (1% O2) in vitro for 24hrs, and n some cases reoxygenated for 24hrs. The expression of E-cadherin, VLA-4 and CXCR4 was analyzed by western blot or flow cytometry. We tested the effect of hypoxia on adhesion of WM cells to BM stroma and fibronectin. We further tested the effect of hypoxia on chemotactic properties of WM cells towards SDF-1 using a transwell migration chamber. In addition, we tested the effect of hypoxia on WM cell survival (by MTT assay), apoptosis and cell cycle (by using AnnexinV-PI and PI, respectively), and signaling pathways associated with survival, apoptosis and cell cycle (by western blotting). Results Tumor progression was shown to increase hypoxic conditions in the BM in vivo. We found a direct correlation between the percent of WM cells in the BM to the level of hypoxia. The level of hypoxia was in a direct correlation with the number of circulating WM cells in vivo. Then we mimicked the hypoxic conditions in vitro and found that cell progression (MTT) and cell cycle (PI staining) were decreased, but apoptosis of WM cells was not affected (AnnexinV-PI staining). These results were confirmed by decreased activation of the PI3K signaling pathway (p-PI3K, p-AKT, p-GSK) and decreased expression of cell cycle proteins (p-Rb, CDK2, CDK4, cyclin-D1 and p-cyclin-E); however, no change was observed in apoptosis-related proteins (PARP, cleaved caspase-3, -8 and -9). Moreover, hypoxia decreased the expression of E-cadherin which contributed to reduction of adhesion of WM cells to the BM stromal cells. At the same time, hypoxic WM cells exhibited increased CXCR4 surface expression and augmented migratory abilities in the presence of SDF-1. Neither the expression of integrins (VLA-4) nor the adhesion of WM cells to fibronectin was affected by hypoxia. This data indicates the conservation of the homing machinery of the WM to the BM despite the hypoxic conditions accompanied by increased chemotactic ability. When hypoxic and normoxic cells were injected to naïve mice, hypoxic cells showed enhanced homing to the BM and tumor colonization. Similarly, hypoxic cells which were reoxygenated in vitro showed more proliferation, cell cycle and activation of proliferative signaling pathways compared to normoxic cells. Conclusions We report that WM tumor growth in the BM increases hypoxia, and that hypoxia induces cell cycle arrest, and less proliferation of cells with no apoptosis. At the same time, hypoxia induces egress of WM cells from the BM through reduction of E-cadherin expression and decreased adhesion. When in the circulation, previously hypoxic cells home more efficiently to the BM through increased expression of CXCR4 and chemotaxis, and through maintaining expression of integrins and adhesion to fibronectin. When in the new oxygenated BM niche, hypoxic WM cells recover and colonize the new niche better than normoxic cells, and reoxygenated hypoxic cells have faster cell cycle and proliferation rate. Disclosures: No relevant conflicts of interest to declare.

scholarly journals AMF1 (GPS2) Modulates p53 Transactivation

2001 ◽  
Vol 21 (17) ◽  
pp. 5913-5924 ◽  
Author(s):  
Yu-Cai Peng ◽  
Felix Kuo ◽  
David E. Breiding ◽  
Yu-Fang Wang ◽  
Claire P. Mansur ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Transcriptional Activation ◽  
Nuclear Factor ◽  
P53 Response ◽  
U2os Cells ◽  
Stress Signals ◽  
Cellular Transcription

ABSTRACT We have reported that the papillomavirus E2 protein binds the nuclear factor AMF1 (also called G-protein pathway suppressor 2 or GPS2) and that their interaction is necessary for transcriptional activation by E2. It has also been shown that AMF1 can influence the activity of cellular transcription factors. These observations led us to test whether AMF1 regulates the functions of p53, a critical transcriptional activator that integrates stress signals and regulates cell cycle and programmed cell death. We report that AMF1 associates with p53 in vivo and in vitro and facilitates the p53 response by augmenting p53-dependent transcription. Overexpression of AMF1 in U2OS cells increases basal level p21WAF1/CIP1 expression and causes a G1 arrest. U2OS cells stably overexpressing AMF1 show increased apoptosis upon exposure to UV irradiation. These data demonstrate that AMF1 modulates p53 activities.

scholarly journals Cell cycle inhibition therapy that targets stathmin in in vitro and in vivo models of breast cancer

2013 ◽  
Vol 20 (5) ◽  
pp. 298-307 ◽  
Author(s):  
C Miceli ◽  
A Tejada ◽  
A Castaneda ◽  
S J Mistry
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
In Vivo Models ◽  
Cell Cycle Inhibition
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