scholarly journals Pectolinarigenin Suppresses the Tumor Growth in Nasopharyngeal Carcinoma

2016 ◽  
Vol 39 (5) ◽  
pp. 1795-1803 ◽  
Author(s):  
Chengyu Wang ◽  
Yin Cheng ◽  
Hongyi Liu ◽  
Yaping Xu ◽  
Hu Peng ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Growth ◽  
Cell Apoptosis ◽  
Severe Toxicity ◽  
Dependent Manner ◽  
Mice Model ◽  
Xenograft Mice Model ◽  
Subcutaneous Xenograft ◽  
Xenograft Mice

Background/Aims: Nasopharyngeal cancer (NPC) is one of the common human malignant diseases all over the world, and chemotherapy remains the main therapy for NPC. However, the survival and life quality of NPC patients are still very poor. Thus, novel and selective anti-tumor agents are pressingly needed. Our previous study identified pectolinarigenin as a novel effective anti-tumor drug candidate for NPC. In this study, we further investigated its anti-tumor activities and explored the potential molecular mechanism. Methods: NPC C666-1 cells were cultured and treated by pectolinarigenin. Cell proliferation assay, colony formation assay, Transwell assay and wound healing assay were conducted and cell apoptosis was detected by flow cytometry. Mitochondrial transmembrane potential and ROS were also observed. NPC subcutaneous xenograft mice model was established to evaluate the anti-tumor effect of pectolinarigenin in vivo. Results: We observed that treatment of pectolinarigenin inhibited cell viability and cell migration of NPC C666-1 cells in concentration- and time-dependent manner. Pectolinarigenin induced cell apoptosis in C666-1 cells detected by flow cytometry analysis, which was associated with the activation of mitochondrial-related apoptosis and the accumulation of reactive oxygen species (ROS). Pectolinarigenin also activated caspase signaling pathway. The in vivo experiment of subcutaneous xenograft mice model also indicated that the administration of pectolinarigenin could decrease the tumor growth of NPC and no severe toxicity was observed. Conclusions: Based on our findings, we conclude that pectolinarigenin could suppress the tumor growth of NPC, which verifies it as a new therapeutic agent for treating this devastating disease.

scholarly journals Knockdown of SNORA47 Inhibits the Tumorigenesis of NSCLC via Mediation of PI3K/Akt Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Huiqing Yu ◽  
Ling Tian ◽  
Liejun Yang ◽  
Shihong Liu ◽  
Sixiong Wang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Apoptosis ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
G1 Arrest ◽  
Mice Model ◽  
Aggressive Cancer ◽  
Xenograft Mice Model ◽  
Nucleolar Rna

BackgroundNon-small cell lung cancer (NSCLC) is a frequently diagnosed aggressive cancer all over the world. Small nucleolar RNAs (snoRNAs) are a group of non-coding mediatory RNAs. A previous report indicated that small nucleolar RNA 47 (SNORA47) is upregulated in NSCLC. However, the role of SNORA47 in NSCLC is unclear.Material and MethodsCell proliferation was measured by immunofluorescence staining. Cell apoptosis and cycle of NSCLC were tested by flow cytometry and the protein expressions were investigated by Western-blot. Meanwhile, cell migration and invasion were detected by transwell assay. Xenograft mice model was established to detect the effect of SNORA47 knockdown on tumor growth of NSLC in vivo.ResultsKnockdown of SNORA47 significantly inhibited the proliferation of NSCLC cells via inducing cell apoptosis. Moreover, migration and invasion of NSCLC cells were notably decreased by SNORA47 shRNA. SNORA47 knockdown significantly induced G1 arrest in NSCLC cells via regulation of p27 Kip1, CDK2, and cyclin D1. Meanwhile, SNORA47 shRNA inhibited EMT process and PI3K/Akt signaling in NSCLC cells. Finally, silencing of SNORA47 significantly inhibited the tumor growth of NSCLC in vivo.ConclusionKnockdown of SNORA47 significantly inhibited the tumorigenesis of NSCLC via inhibition of PI3K/Akt signaling and EMT process. Thereby, our finding might shed a new light on exploring the strategies for the treatment of NSCLC.

scholarly journals Co-Treatment with the Epigenetic Drug, 3-Deazaneplanocin A (DZNep) and Cisplatin after DZNep Priming Enhances the Response to Platinum-Based Therapy in Chondrosarcomas

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4648
Author(s):  
Eva Lhuissier ◽  
Juliette Aury-Landas ◽  
Marion Lenté ◽  
Karim Boumediene ◽  
Catherine Baugé
Keyword(s):  
Tumor Volume ◽  
Mice Model ◽  
Antitumoral Effect ◽  
Viable Cells ◽  
Epigenetic Drug ◽  
Xenograft Mice Model ◽  
Xenograft Mice ◽  
Tumoral Cells

Background: We have previously shown that 3-Deazaneplanocin A (DZNep) induces apoptosis in chondrosarcomas. Herein, we tested whether the combination of this epigenetic drug to a standard anticancer therapy may enhance the response to each drug in these bone tumors. Methods: Two chondrosarcoma cell lines (SW1353 and JJ012) were cultured in the presence of DZNep and/or cisplatin. Cell growth was evaluated by counting viable cells, and apoptosis was determined by Apo2.7 expression by flow cytometry. In vivo, the antitumoral effect of the DZNep/cisplatin combination was assessed through measurements of tumor volume of JJ012 xenografts in nude mice. Results: In vitro, the DZNep/cisplatin combination reduced cell survival and increased apoptosis compared to each drug alone in chondrosarcomas, but not in normal cells (chondrocytes). This enhancement of the antitumoral effect of the DZNep/cisplatin combination required a priming incubation with DZNep before the co-treatment with DZNep/cisplatin. Furthermore, in the chondrosarcoma xenograft mice model, the combination of both drugs more strongly reduced tumor growth and induced more apoptosis in tumoral cells than each of the drugs alone. Conclusion: Our results show that DZNep exposure can presensitize chondrosarcoma cells to a standard anticancer drug, emphasizing the promising clinical utilities of epigenetic-chemotherapeutic drug combinations in the future treatment of chondrosarcomas.

scholarly journals A Bioreductive Prodrug of Cucurbitacin B Significantly Inhibits Tumor Growth in the 4T1 Xenograft Mice Model

2019 ◽  
Vol 10 (10) ◽  
pp. 1400-1406 ◽  
Author(s):  
Parichat Suebsakwong ◽  
Jie Wang ◽  
Phorntip Khetkam ◽  
Natthida Weerapreeyakul ◽  
Jing Wu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mice Model ◽  
Cucurbitacin B ◽  
Xenograft Mice Model ◽  
Xenograft Mice

scholarly journals Artesunate induces mitochondria-mediated apoptosis of human retinoblastoma cells by upregulating Kruppel-like factor 6

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Ying Yang ◽  
Nandan Wu ◽  
Yihui Wu ◽  
Haoting Chen ◽  
Jin Qiu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Apoptosis ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Chemotherapeutic Drug ◽  
Sprague Dawley ◽  
Fundus Fluorescein Angiography ◽  
Intravitreal Chemotherapy ◽  
Vitreous Seeds

Abstract Retinoblastoma (RB) is the most common primary intraocular malignancy in children. Intravitreal chemotherapy achieves favorable clinical outcomes in controlling RB vitreous seeds, which are a common reason for treatment failure. Thus, a novel, effective and safe intravitreal chemotherapeutic drug is urgently required. The malaria drug artesunate (ART) recently demonstrated remarkable anticancer effects with mild side effects. The purpose of this study is to investigate the anti-RB efficacy, the underlying mechanism and the intraocular safety of ART. Herein, we verified that ART inhibits RB cell viability and induces cell apoptosis in a dose- and time-dependent manner. Microarray analysis revealed that Kruppel-like factor 6 (KLF6) was upregulated after ART treatment, and this was further confirmed by real-time PCR and western blot assays. Silencing of KLF6 expression significantly reversed ART-induced RB cell growth inhibition and apoptosis. Furthermore, ART activated mitochondria-mediated apoptosis of RB cells, while silencing KLF6 expression significantly inhibited this effect. In murine xenotransplantation models of RB, we further confirmed that ART inhibits RB tumor growth, induces tumor cell apoptosis and upregulates KLF6 expression. In addition, KLF6 silencing attenuates ART-mediated inhibition of tumor growth in vivo. Furthermore, we proved that intravitreal injection of ART in Sprague-Dawley (SD) rats is safe, with no obvious retinal function damage or structural disorders observed by electrophysiology (ERG), fundal photographs, fundus fluorescein angiography (FFA) or optical coherence tomography (OCT) examinations. Collectively, our study revealed that ART induces mitochondrial apoptosis of RB cells via upregulating KLF6, and our results may extend the application of ART to the clinic as an effective and safe intravitreal chemotherapeutic drug to treat RB, especially RB with vitreous seeds.

scholarly journals Cinobufagin Induces Apoptosis in Osteosarcoma Cells Via the Mitochondria-Mediated Apoptotic Pathway

2018 ◽  
Vol 46 (3) ◽  
pp. 1134-1147 ◽  
Author(s):  
Guo Dai ◽  
Di Zheng ◽  
Weichun Guo ◽  
Jian Yang ◽  
An-yuan Cheng
Keyword(s):  
Cell Apoptosis ◽  
Xenograft Model ◽  
Childhood And Adolescence ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Apoptosis Pathway ◽  
Subcutaneous Xenograft ◽  
Induced Apoptosis

Background/Aims: Osteosarcoma is a common primary malignant bone tumor that mainly occurs in childhood and adolescence. Despite developments in the diagnosis and treatment of osteosarcoma, the prognosis is still very poor. Cinobufagin is an active component in the anti-tumor Chinese medicine called “Chan Su”, and we previously revealed that cinobufagin induced apoptosis and reduced the viability of osteosarcoma cells; however, the underlying mechanism remains to be elucidated. Herein, the present study was undertaken to illuminate the molecular mechanism of cinobufagin-induced apoptosis of osteosarcoma cell. Methods: U2OS and 143B cells were treated with different concentrations of cinobufagin. Cell viability, colony formation ability and morphological changes were assessed by a CCK-8 assay, a clonogenic assay and light microscopy, respectively. Cell apoptosis was detected by Hoechst 33258 and Annexin V-FITC/PI staining. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were determined by flow cytometry. Glutathione (GSH) levels were detected by a GSH and GSSG assay kit. The levels of apoptosis-related proteins were determined by western blotting, and 143B cells were introduced to establish a xenograft tumor model. The effect of cinobufagin on osteosarcoma was further investigated in vivo. Results: Our results showed that cinobufagin significantly reduced the viability of U2OS and 143B cells in vitro in a dose-and time-dependent manner. In addition, cinobufagin-induced apoptosis in U2OS and 143B cells was concentration-dependent. Moreover, we found that cinobufagin treatment increased the level of intracellular ROS, decreased ΔΨm, reduced GSH and inhibited GSH reductase (GR). The effects of cinobufagin on cell proliferation, apoptosis, ROS generation and ΔΨm loss were dramatically reversed when the cells were pretreated with the thiol-antioxidants NAC or GSH. Moreover, cinobufagin treatment increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptitic protein Bcl-2, thus altering the ratio of Bax to Bcl-2. Furthermore, Cinobufagin treatment caused cytochrome c release from the mitochondria to cytoplasm, thus increasing the protein levels of cleaved-caspase family members to induce apoptosis. Ac-DEVD-CHO or Z-LEHD-FMK significantly reduced cinobufagin-induced apoptosis. Finally, a subcutaneous xenograft animal study verified that cinobufagin also significantly suppressed osteosarcoma growth in vivo. Conclusions: Our present data demonstrated that cinobufagin triggered cell apoptosis in osteosarcoma cells via the intrinsic mitochondria-dependent apoptosis pathway by the accumulation of ROS and the loss of ΔΨm. In an in vivo subcutaneous xenograft model, cinobufagin exhibited excellent tumor inhibitory effects. These results suggest that cinobufagin might potentially be further developed as an anti-tumor candidate for treating osteosarcoma patients in the clinic.

scholarly journals Targeting Myc and Hdac8 with a Combination of SiRNAs Inhibits Tumor Growth in a Murine Neuroblastoma Xenograft Model

2020 ◽  
Vol 6 (1) ◽  
pp. 301-307
Author(s):  
Prashad N
Keyword(s):  
Nervous System ◽  
Tumor Growth ◽  
Neuroblastoma Cells ◽  
Xenograft Model ◽  
Mice Model ◽  
Xenograft Mice Model ◽  
Mycn Expression ◽  
Xenograft Mice ◽  
Combination Of Sirnas

Neuroblastoma is a common tumor of the peripheral nervous system in children. Highly aggressive MYC-drivenneuroblastoma is defined by increased MYC and/or MYCN expression. HDAC8 overexpression is associated with advanced neuroblastoma. Previously, we have demonstrated that transient knockdown of both Myc and Hdac8 using siRNA significantly suppressed neuroblastoma cells proliferation compared to knockdown of either target in vitro. In this study, we further investigated whether combinational targeting Myc and Hdac8 in neuroblastoma xenograft mice model is consistent with our previous findings. Intratumoral treatment with siRNA-MYC and siRNA-HDAC8 reduced the levels of the target MYC protein by 64% and HDAC8 by 85%; in addition, we found that the average tumor growth was reduced by 80% compared to that of control tumors treated with NC-siRNA. Our results suggest the potential therapeutic effect of the combination of siRNA-MYC and siRNA-HDAC8 for neuroblastoma treatment.

scholarly journals Knockdown of 91 H Suppresses the Tumorigenesis of Osteosarcoma via Inducing Methylation of CDK4 Promoter

2021 ◽  
Vol 20 ◽  
pp. 153303382199000
Author(s):  
Suoli Cheng ◽  
Jianping Zheng ◽  
Xueqin Liu ◽  
Jiandang Shi ◽  
Fan Gong ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Migration And Invasion ◽  
G1 Arrest ◽  
Osteosarcoma Cells ◽  
Mice Model ◽  
Primary Malignancy ◽  
Specific Pcr ◽  
Xenograft Mice Model

Background: Osteosarcoma is the most leading primary malignancy of the bone in adolescents all over the world. Long non-coding RNA (lncRNA) 91 H has been reported to participated in multiple cancers. Meanwhile, lncRNA 91 H has been proved to be upregulated in osteosarcoma. However, the function of 91 H in osteosarcoma remains unclear. Methods: Gene and protein expressions in osteosarcoma cells were detected by qRT-PCR and western blot, respectively. Cell viability was tested by CCK-8 assay. Ki67 staining was used to measure cell proliferation. Cell apoptosis and cycle were assessed by flow cytometry. In addition, transwell assay was used to detect cell migration and invasion. Furthermore, Methylation-specific PCR (MSP) was performed to test the methylation of CDK4 promoter. Finally, xenograft mice model was established to explore the role of 91 H in osteosarcoma in vivo. Results: Knockdown of 91 H significantly inhibited the growth of osteosarcoma cells via inducing the cell apoptosis. In addition, 91 H siRNA notably suppressed the migration and invasion of osteosarcoma cells. Meanwhile, knockdown of 91 H inhibited the progression of osteosarcoma via inducing methylation of CDK4 promoter. Furthermore, 91 H knockdown obviously induced G1 arrest in osteosarcoma cells via inhibition of PCNA and Cyclin D1. Finally, knockdown of 91 H notably inhibited the tumor growth of osteosarcoma in vivo. Conclusion: knockdown of 91 H suppressed the tumorigenesis of osteosarcoma via inducing methylation of CDK4 promoter in vitro and in vivo. Thus, 91 H may serve as a new target for the treatment of osteosarcoma.

scholarly journals The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1268 ◽  
Author(s):  
Kuan-Lin Kuo ◽  
Shing-Hwa Liu ◽  
Wei-Chou Lin ◽  
Po-Ming Chow ◽  
Yu-Wei Chang ◽  
...  
Keyword(s):  
Antitumor Effect ◽  
Enzyme Inhibitor ◽  
Critical Role ◽  
Deubiquitinating Enzymes ◽  
Mice Model ◽  
Bladder Urothelial Carcinoma ◽  
Xenograft Mice Model ◽  
Xenograft Mice

After chemotherapy for the treatment of metastatic bladder urothelial carcinoma (UC), most patients inevitably encounter drug resistance and resultant treatment failure. Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins and play a critical role in maintaining protein homeostasis. This study investigated the antitumor effect of PR-619, a DUBs inhibitor, in combination with cisplatin, for bladder UC treatment. Our results showed that PR-619 effectively induced dose- and time-dependent cytotoxicity, apoptosis, and ER-stress related apoptosis in human UC (T24 and BFTC-905) cells. Additionally, co-treatment of PR-619 with cisplatin potentiated cisplatin-induced cytotoxicity in UC cells and was accompanied by the concurrent suppression of Bcl-2. We also proved that Bcl-2 overexpression is related to the chemo-resistant status in patients with metastatic UC by immunohistochemistry (IHC) staining. In a xenograft mice model, we confirmed that PR-619 enhanced the antitumor effect of cisplatin on cisplatin-naïve and cisplatin-resistant UCs. Our results demonstrated that PR-619 effectively enhanced the cisplatin-induced antitumor effect via concurrent suppression of the Bcl-2 level. These findings provide promising insight for developing a therapeutic strategy for UC treatment.

scholarly journals Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Livan Delgado-Roche ◽  
Kethia González ◽  
Fernando Mesta ◽  
Beatriz Couder ◽  
Zaira Tavarez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Activity ◽  
Thalassia Testudinum ◽  
Ros Generation ◽  
Mice Model ◽  
Marine Plant ◽  
Colorectal Cancer Cells ◽  
Xenograft Mice Model ◽  
Xenograft Mice

Marine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained from Thalassia testudinum marine plant and thalassiolin B in human colorectal cancer cells. Human cancer cell lines, including HCT15, HCT116, SW260, and HT29 were treated with tested products for cytotoxicity evaluation by crystal violet assay. The potential proapoptotic effect of these natural products was assessed by flow cytometry in HCT15 cells at 48 h using Annexin V-FITC/propidium iodide. In addition, reactive oxygen species (ROS) generation was measured by fluorescence using DCFH-DA staining, and sulfhydryl concentration by spectrophotometry. The in vivo antitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice. In vivo proapoptotic effect was also evaluated by immunohistochemistry using anti-caspase 3 and anti-Bcl-2 antibodies. The results showed that tested products exert colorectal cancer cell cytotoxicity. Besides, the tested products induced a significant increase (p < 0.05) of intracellular ROS generation, and a depletion of sulfhydryl concentration in HCT15 cells. The polyphenolic fraction arrested tumor growth and induced apoptosis in the xenograft mice model. These results demonstrate the cytotoxic activity of T. testudinum metabolites associated, at least, with ROS overproduction and pro-apoptotic effects. Here we demonstrated for the first time the antitumor activity of a T. testudinum polar extract in a xenograft mice model. These results suggest the potential use of T. testudinum marine plant metabolites as adjuvant treatment in cancer therapy.

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