397 Development of a doxycycline-dependent caspase 3 death switch model to assess the immune response to rapid and synchronous tumour cell apoptosis in vivo

2010 ◽  
Vol 8 (5) ◽  
pp. 101-102
Author(s):  
M. Melis ◽  
K. Simpson ◽  
J. Honeychurch ◽  
A. Weldman ◽  
M. MacFarlane ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumour Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Synchronous Tumour

scholarly journals Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jian-Xing Wang ◽  
Xin-Ju Jia ◽  
Yan Liu ◽  
Jin-Hui Dong ◽  
Xiu-Min Ren ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Laryngeal Squamous Cell Carcinoma

Abstract Background Increasing evidence has suggested that microRNAs (miRNAs) act as key post-transcriptional regulators in tumor progression. Previous studies have confirmed that miR-17-5p functions as an oncogene in multiple cancers and contributes to tumor progression. However, the role and biological functions of miR-17-5p in the development of laryngeal squamous cell carcinoma (LSCC) still remain unknown. Methods qRT-PCR was used to detect miRNA and mRNA expression levels in LSCC tissues and cell lines. CCK-8 assay was used to measure cell viability and flow cytometry was performed to evaluate cell apoptosis. Western blot analysis was used to detect the protein levels of BAX, BCL-2, cleaved Caspase-3, PIK3R1 and AKT. Luciferase reporter assay was used to detect the effect of miR-17-5p on PIK3R1 expression. Xenograft animal model was used to test the effect of miR-17-5p on LSCC cell in vivo. Results In the present study, we found that miR-17-5p expression level was upregulated in LSCC tissues and cell lines. Depletion of miR-17-5p in LSCC cells significantly reduced cell proliferation and promoted cell apoptosis in vitro and in vivo. Mechanically, knockdown of miR-17-5p in LSCC cells inhibited BCL-2 expression while enhanced BAX and cleaved Caspase-3 protein expression. Moreover, depletion of miR-17-5p in LSCC cells suppressed AKT phosphorylation but did not influence PTEN expression. Importantly, miR-17-5p positively regulated PIK3R1 expression by directly binding to its 3′-untranslated region (UTR). Additionally, PIK3R1, which expression was downregulated in LSCC tissues and cell lines, was involved in LSCC cell survival by modulating the activation of AKT signal pathway. Dysregulation of miR-17-5p/PIK3R1 axis was participated in LSCC cell proliferation and apoptosis by inhibiting the activation of the PI3K/AKT signaling pathway. Conclusions In conclusion, our study indicates that the miR-17-5p/PIK3R1 axis plays an essential role in the development of LSCC and provides a potential therapeutic target for LSCC treatment.

scholarly journals Anti-bacterial and anti-viral nanchangmycin displays anti-myeloma activity by targeting Otub1 and c-Maf

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Yujia Xu ◽  
Tong Sun ◽  
Kun Zeng ◽  
Min Xu ◽  
Jinhao Chen ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Caspase 3 ◽  
Plasma Cells ◽  
Mrna Level ◽  
Annexin V ◽  
Safety And Efficacy ◽  
In Vivo Assays ◽  
Subsequent Degradation ◽  
Factor C

Abstract As a deubiqutinase Otub1 stabilizes and promotes the oncogenic activity of the transcription factor c-Maf in multiple myeloma (MM), a malignancy of plasma cells. In the screen for bioactive inhibitors of the Otub1/c-Maf axis for MM treatment, nanchangmycin (Nam), a polyketide antibiotic, was identified to suppress c-Maf activity in the presence of Otub1. By suppressing Otub1, Nam induces c-Maf polyubiquitination and subsequent degradation in proteasomes but does not alter its mRNA level. Consistently, Nam downregulates the expression of CCND2, ARK5, and ITGB7, the downstream genes regulated by c-Maf, and promotes MM cell apoptosis as evidenced by PARP and Caspase-3 cleavage, as well as Annexin V staining. In line with the hypothesis, overexpression of Otub1 partly rescues Nam-induced MM cell apoptosis, and interestingly, when Otub1 is knocked down, Nam-decreased MM cell survival is also partly ablated, suggesting Otub1 is essential for Nam anti-MM activity. Nam also displays potent anti-MM activity synergistically with Doxorubicin or lenalidomide. In the in vivo assays, Nam almost completely suppresses the growth of MM xenografts in nude mice at low dosages but it shows no toxicity. Given its safety and efficacy, Nam has a potential for MM treatment by targeting the Otub1/c-Maf axis.

scholarly journals Sustained tumour eradication after induced caspase-3 activation and synchronous tumour apoptosis requires an intact host immune response

2013 ◽  
Vol 20 (5) ◽  
pp. 765-773 ◽  
Author(s):  
M H M Melis ◽  
K L Simpson ◽  
S J Dovedi ◽  
A Welman ◽  
M MacFarlane ◽  
...  
Keyword(s):  
Immune Response ◽  
Caspase 3 ◽  
Host Immune Response ◽  
Synchronous Tumour

Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways

Blood ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 5455-5462 ◽  
Author(s):  
Michael Wang ◽  
Liang Zhang ◽  
Xiaohong Han ◽  
Jing Yang ◽  
Jianfei Qian ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
Caspase 9 ◽  
Mantle Cell ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor

Abstract Atiprimod is a novel cationic amphiphilic compound and has been shown to exert antimyeloma effects both in vitro and in mouse experiments. This study was undertaken to evaluate the therapeutic efficacy of atiprimod on mantle cell lymphoma (MCL) and elucidate the mechanism by which it induces cell apoptosis. Atiprimod inhibited the growth and induced apoptosis of MCL cell lines and freshly isolated primary tumor cells in vitro. More importantly, atiprimod significantly inhibited tumor growth in vivo and prolonged the survival of tumor-bearing mice. However, atiprimod also exhibited lower cytotoxicity toward normal lymphocytes. Atiprimod activated c-Jun N-terminal protein kinases (JNK) and up-regulated the level of Bax, Bad, and phosphorylated Bcl-2, resulting in release of apoptosis-inducing factor (AIF) and cytochrome c from mitochondria and activation and cleavage of caspase-9, caspase-3, and PARP. However, AIF, but not activation of caspases or PARP, was responsible for apoptosis in MCL cells because an AIF inhibitor, but not pan-caspase or paspase-9 inhibitors, completely abrogated atiprimod-induced apoptosis. Taken together, our results demonstrate that atiprimod displays a strong anti-MCL activity. Cell apoptosis was induced mainly via activation of the AIF pathway. These results support the use of atiprimod as a potential agent in MCL chemotherapy.

scholarly journals Anticancer effects of dihydromyricetin on the proliferation, migration, apoptosis and in vivo tumorigenicity of human hepatocellular carcinoma Hep3B cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lianggui Jiang ◽  
Wen-Chu Ye ◽  
Zuobiao Li ◽  
Yongguang Yang ◽  
Wei Dai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Public Health Problem ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Anticancer Effect ◽  
Caspase 9 ◽  
Hep3b Cells

Abstract Background Hepatocellular carcinoma (HCC) represents a serious public health problem worldwide and has high morbidity and mortality. Dihydromyricetin (DHM) exhibits anticancer effect on a variety of malignancies, but its anticancer function of DHM in HCC has been unclear. The aim of this study was designed to investigate the anticancer effect of DHM on cell apoptosis, proliferation, migration and invasion of hepatoma carcinoma cells. Methods Cultured Hep3B cells were treated with different DHM concentrations, followed by cell apoptosis, proliferation, migration and invasion were examined by CCK-8, colony formation assay, wound healing, Transwell and flow cytometry, respectively. The mRNA and protein expression of BCL-2, Cleaved-caspase 3, Cleaved-caspase 9, BAK, BAX and BAD were validated by western blot. Results DHM markedly suppressed proliferation, migration, invasion and facilitated apoptosis in Hep3B cells. Mechanistically, DHM significantly downregulated the Bcl-2 expression, and upregulated the mRNA and protein levels of Cleaved-Caspase 3, Cleaved- Caspase 9, Bak, Bax and Bad. Furthermore, in the nude mice tumorigenic model, DHM treatment greatly decreased the weight of the HCC cancers compared to the weights in control and NDP group. Conclusions DHM could suppress cell proliferation, migration, invasion, and facilitated apoptosis in Hep3B cells. These findings could provide novel insights to develop potential therapeutic strategy for the clinical treatment of HCC.

scholarly journals Antitumor activity of gambogic acid lysinate in human SiHa cells in vitro and in vivo

2021 ◽  
Author(s):  
Jie Niu ◽  
Jingyu Sun ◽  
Yahua Liu ◽  
Jun Guo ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Body Weight ◽  
Antitumor Activity ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Siha Cell ◽  
G1 Phase ◽  
Gambogic Acid ◽  
Siha Cells

Abstract Background: Cervical cancer is a major cause of death for women worldwide and human papillomavirus (HPV) infection is the main cause of cervical cancer. The purpose of this study was to explore the anti-tumor activity of gambogic acid lysinate and clarify its mechanism in SiHa cells. Methods: In the present study, cell viability was detected by means of an MTT assay, a cell growth curve was drawn with Microsoft Excel 2010, the cell cycle and cell apoptosis were evaluated by flow cytometry, Western blotting was employed to explore the mechanism of gambogic acid lysinate, and caspase-3 activity was determined with a colorimetric Caspase-3 assay kit. Additionally, the in vivo antitumor activity of gambogic acid lysinate was studied through a xenograft tumor model established with nude mice. Results: The results showed that gambogic acid lysinate inhibited the proliferation of both SiHa cells (half-maximal inhibitory concentration (IC50) values: 0.83 μmol/l and 0.77 μmol/l for 48 h and 72 h) and HeLa cells (IC50 >2 μmol/l). In SiHa cells, gambogic acid lysinate (1 and 2 μmol/l) inhibited cell proliferation and 2 μmol/l gambogic acid lysinate induced cell apoptosis and decreased the number of S phase cells. Both 1 and 2 μmol/l gambogic acid lysinate increased the number of G0/G1 phase cells. The results of a Western blot assay demonstrated that P53 and P21 were involved in SiHa cell G0/G1 phase arrest and that Bcl-2 and BAX were involved in SiHa cell apoptosis. An in vivo study showed that the growth of SiHa cell xenograft tumors was inhibited by gambogic acid lysinate (2.5 mg/kg body weight), however, gambogic acid lysinate (2.5 mg/kg body weight) had no significant effect on mouse weight gain. Conclusions: gambogic acid lysinate is a promising candidate for cervical cancer therapy.

scholarly journals Huxie Huaji Ointment Induced Apoptosis of Liver Cancer Cells In Vivo and In Vitro by Activating the Mitochondrial Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yuan Cai ◽  
Qing Du ◽  
Tian-Hao Deng ◽  
Bing-Bing Shen ◽  
Yan-Mei Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Hepg2 Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Cell Counting ◽  
Cyt C

Huxie Huaji (HXHJ) Ointment is a famous traditional Chinese medicinal prescription and is commonly used for the clinical treatment of hepatocellular carcinoma by boosting immunity and detoxification. However, the scientific evidence for the effect of HXHJ Ointment on hepatocellular carcinoma and the underlying molecular mechanism are lacking. The present study aimed to identify the effects of HXHJ Ointment on hepatocellular carcinoma in vitro and in vivo as well as investigating the mechanistic basis for the anticancer effect of HXHJ ointment. First, liquid chromatography-mass spectrometry was used to verify the composition of HXHJ Ointment and quality control. Second, in vitro, Cell Counting Kit (CCK8) cell viability assay and Hoechst 33342 staining assay were performed to explain the cell apoptosis. The protein levels of tumor suppressor protein (p53), B-cell lymphoma 2 gene (Bcl-2), cytochrome C (Cyt-C), and aspartate proteolytic enzyme-3 (caspase-3) were examined by immunofluorescence. Finally, in vivo, hematoxylin and eosin (H&E) staining was used to observe the pathological changes in hepatocellular carcinoma samples. Western blots and immunohistochemistry were used to detect the anticancer properties of HXHJ ointment. The results in vitro showed that 20% HXHJ Ointment serum could significantly inhibit HepG2 cell proliferation, increased tumor suppressor gene p53, downregulated antiapoptotic protein Bcl-2, promoted the release of mitochondrial Cyt-C, activated caspase-3, and induced HepG2 cell apoptosis. Furthermore, in vivo experiments showed that HXHJ Ointment could effectively inhibit tumor growth in nude mice xenotransplanted with HepG2 cells, changed the morphology of tumor cells, and regulated the expression of apoptosis-related protein pathway p53/Bcl-2/Cyt-C/caspase-3. HXHJ Ointment can significantly inhibit the development of hepatocellular carcinoma, and its mechanism may be related to the regulation of p53/Bcl-2/Cyt-C/caspase-3 signaling pathway to induce cell mitochondrial apoptosis.

scholarly journals In Vitro and in Vivo Scolicidal Activities of Holothuria leuco-spilota Extract and CeO2 Nanoparticles against Hydatid Cyst

2019 ◽  
Author(s):  
Safa ARYAMAND ◽  
Shahram KHADEMVATAN ◽  
Khosrow HAZRATI TAPPEH ◽  
Behnam HESHMATIAN ◽  
Ali JELODAR
Keyword(s):  
Hydatid Cyst ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Ceo2 Nanoparticles ◽  
Hydatid Cysts ◽  
Hydatid Fluid ◽  
Cyst Development

Background: We aimed to investigate the scolicidal effects of Holothuria leucospilota extract and CeO2 nanoparticles against protoscoleces of hydatid cysts in-vitro and in-vivo. Methods: Hydatid cysts were collected from, Urmia slaughterhouses between years 2016-2017 and the hydatid fluid aspirated from the fertile cysts. Various concentration of H. leucospilota extract, CeO2 NPs and combination of CeO2-NPs/H. leucospilota were used for 10-60 min to evaluate the viability of protoscoleces by 0.1% eosin method. CASPASE -3 activity measured for assessment of cell apoptosis in treated protoscoleces. BALB/c mice were infected intraperitoneally with 2000 viable protoscoleces and treated daily for 4 wk by intragastrical inoculation with H. leucospilota, CeO2 NPs, combination of CeO2 NPs/H. leucospilota and Albendazole. Cyst development was macroscopically analyzed. Results: H. leucospilota extract and combination of CeO2 NPs/H. leucospilota have potent scolicidal activity at concentration of 20 mg/ml and 15 mg/ml after 60 min treatment. Maximum caspase-3 activity was observed when protoscoleces expose with H. leucospilota and combination H. leucospilota & CeO2 NPs. After treatment of cyst infected mice with extract and CeO2 NPs, combination of CeO2 NPs/H leucospilota and albendazole, a significant decrease in number of cysts, size and volume of cyst (P<0.05) was observed. Conclusion: This result shows an antihydatic and scolicidal effects of H. leucospilota extract and CeO2 NPs.

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