26 results on '"An, Xinyou"'
Search Results
2. Nicotinamide N-methyltransferase inhibits autophagy induced by oxidative stress through suppressing the AMPK pathway in breast cancer cells
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Yanzhong Wang, Guoli Li, Haitao Yu, Jin Zeng, Xi Zhou, Jun Yang, Xinyou Xie, Jun Zhang, and Xucheng Huang
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AMPK ,Cancer Research ,Cell ,Nicotinamide N-methyltransferase ,medicine.disease_cause ,lcsh:RC254-282 ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Cellular stress response ,Genetics ,medicine ,Autophagy ,lcsh:QH573-671 ,030304 developmental biology ,ULK1 ,0303 health sciences ,Gene knockdown ,medicine.diagnostic_test ,Chemistry ,lcsh:Cytology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.anatomical_structure ,Oncology ,Apoptosis ,Oxidative stress ,030220 oncology & carcinogenesis ,Cancer research ,Primary Research - Abstract
Background Nicotinamide N-methyltransferase (NNMT) is highly expressed in several cancers and can regulate cell epigenetic status and various cell metabolism pathways, such as ATP synthesis and cellular stress response. We reported in our previous papers that NNMT overexpression inhibits the apoptosis and enhances the chemotherapy resistance of breast cancer cells. This study aims to investigate the effect of NNMT on autophagy induced by oxidative stress in breast cancer cells, which might provide a novel therapeutic strategy for breast cancer treatment. Methods NNMT and LC3B II protein levels in the two cell models (SK-BR-3 and MDA-MB-231) with NNMT overexpression or knockdown were detected by Western blotting and correlated with each other. Changes in cellular viability, intracellular reactive oxygen species (ROS) and ATP levels were assessed after H2O2 treatment. Then, autophagosomes were imaged by transmission electron microscopy, and LC3 puncta were examined by confocal microscopy and flow cytometry. The LC3B II level and AMPK-ULK1 pathway activity were both detected by Western blotting to determine the role of NNMT in the H2O2-induced autophagy. Results NNMT expression was negatively correlated with LC3B II expression in both cell models (SK-BR-3 and MDA-MB-231). Then, NNMT overexpression attenuated the autophagy induced by H2O2 in SK-BR-3 cells, whereas knockdown promoted autophagy induced by H2O2 in MDA-MB-231 cells. Furthermore, mechanistic studies showed that NNMT suppressed the ROS increase, ATP decrease and AMPK-ULK1 pathway activation, resulting in the inhibition of H2O2-induced autophagy in breast cancer cells. Conclusions We conclude that NNMT inhibits the autophagy induced by oxidative stress through the ROS-mediated AMPK-ULK1 pathway in breast cancer cells and may protect breast cancer cells against oxidative stress through autophagy suppression.
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- 2020
3. Resistance of peanut to web blotch caused by Phoma arachidicola is related to papillae formation and the hypersensitive response.
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Sun, Ziqi, Cheng, Yujie, Qi, Feiyan, Zhang, Mengyuan, Tian, Mengdi, Wang, Juan, Wu, Xiaohui, Huang, Bingyan, Dong, Wenzhao, Zhang, Xinyou, and Zheng, Zheng
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PEANUTS ,PEANUT breeding ,PHOMA ,APOPTOSIS ,ARACHIS - Abstract
Peanut (Arachis hypogaea) is an important economic crop that is susceptible to various foliar diseases. Web blotch, which is caused by Phoma arachidicola, is one of the most serious peanut foliar diseases because it affects the leaves and results in substantial yield losses. In this study, the P. arachidicola infection process and the response of peanut plants to infection were revealed through a cytological study of resistant and susceptible peanut varieties. Conidial germination rates, appressorium formation and resistance responses, including papillae formation and the hypersensitive response (HR), were analysed at different infection stages. Notably, the basal infection response of susceptible varieties resulted in limited papillae formation and a single HR, which was followed by programmed cell death. The papillae formation frequency and HR frequency were significantly greater in the resistant varieties than in the susceptible varieties at 84 h postinoculation. The primary difference between the two resistant varieties was the superior HR of Zheng8903 compared with that of Yuhua15. The complex amphidiploid peanut genome may explain the complexity and diversity of the resistance responses. The interactions of functional orthologs should be clarified and perhaps modulated in future investigations. The results of this study revealed the differences in the resistance responses among peanut germplasm and may be relevant for the breeding of new peanut varieties highly resistant to P. arachidicola. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Curcumin Reverses NNMT-Induced 5-Fluorouracil Resistance via Increasing ROS and Cell Cycle Arrest in Colorectal Cancer Cells
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Jun Zhang, Jun Yang, Yejia Li, Haitao Yu, Guoli Li, Lifen Chen, Xiao Shao, Sining Fang, Qingchao Tong, Xinyou Xie, Yanzhong Wang, and Beibei Kong
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Male ,STAT3 Transcription Factor ,Cell cycle checkpoint ,Curcumin ,Colorectal cancer ,Down-Regulation ,Mice, Nude ,Nicotinamide N-methyltransferase ,Apoptosis ,colorectal cancer ,Biochemistry ,Microbiology ,Article ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,nicotinamide N-methyltransferase ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Phosphorylation ,Molecular Biology ,Cell Proliferation ,chemistry.chemical_classification ,Reactive oxygen species ,Mice, Inbred BALB C ,Chemistry ,Cell growth ,chemoresistance ,Drug Synergism ,Cell Cycle Checkpoints ,medicine.disease ,Xenograft Model Antitumor Assays ,QR1-502 ,Cell culture ,cell cycle arrest ,Cancer research ,Fluorouracil ,Colorectal Neoplasms ,Reactive Oxygen Species - Abstract
Nicotinamide N-methyltransferase (NNMT) plays multiple roles in improving the aggressiveness of colorectal cancer (CRC) and enhancing resistance to 5-Fluorouracil (5-FU), making it an attractive therapeutic target. Curcumin (Cur) is a promising natural compound, exhibiting multiple antitumor effects and potentiating the effect of 5-FU. The aim of the present study is to explore the effect of Cur on attenuating NNMT-induced resistance to 5-FU in CRC. A panel of CRC cell lines with different NNMT expressions are used to characterize the effect of Cur. Herein, it is observed that Cur can depress the expression of NNMT and p-STAT3 in CRC cells. Furthermore, Cur can induce inhibition of cell proliferation, G2/M phase cell cycle arrest, and reactive oxygen species (ROS) generation, especially in high-NNMT-expression CRC cell lines. Cur can also re-sensitize high-NNMT-expression CRC cells to 5-FU both in vitro and in vivo. In summary, it is proposed that Cur can reverse NNMT-induced cell proliferation and 5-FU resistance through ROS generation and cell cycle arrest. Given that Cur has long been used, we suppose that Cur is a promising anticancer drug candidate with minimal side effects for human CRC therapy and can attenuate NNMT-induced resistance to 5-FU.
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- 2021
5. Nicotinamide N-methyltransferase enhances chemoresistance in breast cancer through SIRT1 protein stabilization
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Shuduo Xie, Gavin Y. Wang, Xinyou Xie, Weiping Wu, Yanzhong Wang, Jie Lu, Haitao Yu, Guoli Li, Jun Zhang, Jin Zeng, Tao Zhu, and Fengying Li
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Survival ,medicine.medical_treatment ,Apoptosis ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer chemotherapy ,Breast cancer ,Sirtuin 1 ,Surgical oncology ,Nicotinamide N-Methyltransferase ,Neoplasm Metastasis ,RNA, Small Interfering ,Gene knockdown ,Protein Stability ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Paclitaxel ,030220 oncology & carcinogenesis ,Female ,RNA Interference ,Protein stabilization ,Breast carcinoma ,Chemoresistance ,Research Article ,Adult ,NNMT ,Nicotinamide N-methyltransferase ,Antineoplastic Agents ,Breast Neoplasms ,Chemotherapy response ,lcsh:RC254-282 ,03 medical and health sciences ,SIRT1 ,Cell Line, Tumor ,medicine ,Biomarkers, Tumor ,Humans ,Mammary Glands, Human ,Aged ,Neoplasm Staging ,Hyperplasia ,Dose-Response Relationship, Drug ,business.industry ,medicine.disease ,chemistry ,Drug Resistance, Neoplasm ,Cancer research ,business - Abstract
Background Nicotinamide N-methyltransferase (NNMT) is overexpressed in various human tumors and involved in the development and progression of several carcinomas. In breast cancer, NNMT was found to be overexpressed in several cell lines. However, the clinical relevance of NNMT in breast cancer is not yet clear. Methods NNMT expression in breast carcinoma was examined by immunohistochemistry, and then, its relationship with patient clinicopathological characteristics was analyzed. The effects of NNMT on chemoresistance in breast cancer cells were assessed by cell viability, colony formation, and apoptosis assay. The NNMT, SIRT1, p53, and acetyl-p53 proteins, which are involved in NNMT-related chemoresistance, were examined by Western blotting. The SIRT1 mRNA was examined by real-time PCR, and its activity was measured by using the SIRT1 deacetylase fluorometric reagent kit. Results NNMT expression was significantly higher (53.9%) in breast carcinoma than in paracancerous tissues (10.0%) and breast hyperplasia (13.3%). A high level of NNMT expression correlated with poor survival and chemotherapy response in breast cancer patients who received chemotherapy. Ectopic overexpression of NNMT significantly inhibited the apoptotic cell death and suppression of colony formation induced by adriamycin and paclitaxel. Mechanistic studies revealed that NNMT overexpression increased SIRT1 expression and promoted its activity. Either inhibition of SIRT1 by EX527 or knockdown of SIRT1 by siRNA could reverse NNMT-mediated resistance to adriamycin and paclitaxel, which suggests that SIRT1 plays a critical role in NNMT-related chemoresistance in breast cancer. Conclusions The results of this study demonstrate a novel correlation between the NNMT expression level and patient survival, suggesting that NNMT has the potential to become a new prognostic biomarker to predict the treatment outcomes of the clinical chemotherapy in breast cancer. Moreover, targeting NNMT or downstream SIRT1 may represent a new therapeutic approach to improve the efficacy of breast cancer chemotherapy. Electronic supplementary material The online version of this article (10.1186/s13058-019-1150-z) contains supplementary material, which is available to authorized users.
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- 2019
6. Repression of Hexokinases II-Mediated Glycolysis Contributes to Piperlongumine-Induced Tumor Suppression in Non-Small Cell Lung Cancer Cells
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Ming Li, Xinyou Yu, Feng Gao, Wei Li, and Li Zhou
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Lung Neoplasms ,piperlongumine ,Immunoblotting ,AKT1 ,Apoptosis ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,chemistry.chemical_compound ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Humans ,Immunoprecipitation ,Glycolysis ,Molecular Biology ,Protein kinase B ,non-small cell lung cancer ,Ecology, Evolution, Behavior and Systematics ,Piperlongumine ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,Chemistry ,Akt ,Intrinsic apoptosis ,Dioxolanes ,Cell Biology ,glycolysis ,Flow Cytometry ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Cancer research ,Hexokinases II ,Signal transduction ,VDAC1 ,Signal Transduction ,Research Paper ,Developmental Biology - Abstract
Deregulation of glycolysis is a common phenomenon in human non-small cell lung cancer (NSCLC). In the present study, we reported the natural compound, piperlongumine, has a profound anti-tumor effect on NSCLC via regulation of glycolysis. Piperlongumine suppressed the proliferation, colony formation and HK2-mediated glycolysis in NSCLC cells. We demonstrated that exposure to piperlongumine disrupted the interaction between HK2 and VDAC1, induced the activation of the intrinsic apoptosis signaling pathway. Moreover, our results revealed that piperlongumine down-regulated the Akt signaling, exogenous overexpression of constitutively activated Akt1 in HCC827 and H1975 cells significantly rescued piperlongumine-induced glycolysis suppression and apoptosis. The xenograft mouse model data demonstrated the pivotal role of suppression of Akt activation and HK2-mediated glycolysis in mediating the in vivo antitumor effects of piperlongumine. The expression of HK2 was higher in malignant NSCLC tissues than that of the paired adjacent tissues, and was positively correlated with poor survival time. Our results suggest that HK2 could be used as a potential predictor of survival and targeting HK2 appears to be a new approach for clinical NSCLC prevention or treatment.
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- 2019
7. Vanillin downregulates NNMT and attenuates NNMT‑related resistance to 5‑fluorouracil via ROS‑induced cell apoptosis in colorectal cancer cells
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Qingchao Tong, Guoli Li, Jun Zhang, Lifen Chen, Yejia Li, Haitao Yu, Xinyou Xie, Jin Zeng, and Beibei Kong
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Cancer Research ,Small interfering RNA ,Cell ,colorectal cancer ,Apoptosis ,Nicotinamide N-methyltransferase ,Small hairpin RNA ,nicotinamide N-methyltransferase ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,ASK1 ,cell apoptosis ,Chemistry ,Cell growth ,chemoresistance ,Articles ,General Medicine ,Cell cycle ,medicine.anatomical_structure ,vanillin ,Oncology ,Drug Resistance, Neoplasm ,Benzaldehydes ,Cancer research ,Fluorouracil ,Drug Screening Assays, Antitumor ,Colorectal Neoplasms ,Reactive Oxygen Species - Abstract
Chemoresistance is the main cause of poor prognosis in colorectal cancer (CRC). Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that is upregulated in various tumor types. It has been reported that NNMT inhibits apoptosis and enhances resistance to 5-fluorouracil (5-Fu) via inhibition of the apoptosis signal regulating kinase 1 (ASK1)-p38 MAPK pathway in CRC cells. A natural product library was screened, and it was found that vanillin, also known as 4-hydroxy-3-methoxybenzaldehyde, a plant secondary metabolite found in several essential plant oils, mainly Vanilla planifolia, Vanilla tahitensis, and Vanilla pompon, may be a promising anticancer compound targeted to NNMT. The aim of the present study was to explore the effect of vanillin on promoting apoptosis and attenuating NNMT-induced resistance to 5-Fu in CRC. Lentiviral vectors of short hairpin RNA and small interfering RNA were transfected into HT-29 cells to construct NNMT-knockdown HT-29 cell lines. Vectors containing an open reading frame of NNMT were stably transfected into SW480 cells to induce NNMT overexpression in SW480 cell lines. Vanillin was found to inhibit the mRNA and protein expression levels of NNMT following the inhibition of NNMT activity in HT-29 cell lines. Vanillin was able to reverse NNMT-induced increased cell proliferation, decreased cell apoptosis and resistance to 5-Fu by inhibiting NNMT expression. Furthermore, it increased cell apoptosis by activating the ASK1-p38 MAPK pathway, which could be inhibited by NNMT. In addition, vanillin increased cell apoptosis by promoting mitochondrial damage and reactive oxygen species. In vivo, the combination of vanillin with 5-Fu yielded a notable synergy in inhibiting tumor growth and inducing apoptosis. Considering that vanillin is an important flavor and aromatic component used in foods worldwide, vanillin is deemed to be a promising anticancer candidate by inhibiting NNMT and may attenuate NNMT-induced resistance to 5-Fu in human CRC therapy with few side effects.
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- 2021
8. Correction: Cullin-5 neddylation-mediated NOXA degradation is enhanced by PRDX1 oligomers in colorectal cancer
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Fengying Li, Qingchao Tong, Yilei Ma, Jin Zeng, Shoufang Xu, Jun Yang, Guoli Li, Jun Zhang, Xinyou Xie, Sining Fang, Jia Liu, and Yanzhong Wang
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Cancer Research ,Ubiquitylation ,Colorectal cancer ,Immunology ,Apoptosis ,Cellular and Molecular Neuroscience ,Ubiquitin ,medicine ,Humans ,lcsh:QH573-671 ,Neddylation ,biology ,lcsh:Cytology ,Chemistry ,Ubiquitination ,Correction ,Peroxiredoxins ,Cell Biology ,Cullin Proteins ,HCT116 Cells ,medicine.disease ,Gene Expression Regulation, Neoplastic ,HEK293 Cells ,Proto-Oncogene Proteins c-bcl-2 ,Proteolysis ,Ubiquitin-Conjugating Enzymes ,biology.protein ,Cancer research ,Protein Multimerization ,Colorectal Neoplasms ,Reactive Oxygen Species ,HT29 Cells ,Cullin ,Half-Life - Abstract
NOXA, a BH3-only proapoptotic protein involved in regulating cell death decisions, is highly expressed but short-lived in colorectal cancer (CRC). Neddylated cullin-5 (CUL5)-mediated ubiquitination and degradation of NOXA is crucial to prevent its overaccumulation and maintain an appropriate action time. However, how this process is manipulated by CRC cells commonly exposed to oxidative stress remain unknown. The peroxiredoxin PRDX1, a conceivable antioxidant overexpressed in CRC tissues, has been shown to inhibit apoptosis and TRAF6 ubiquitin-ligase activity. In this study, we found that PRDX1 inhibits CRC cell apoptosis by downregulating NOXA. Mechanistically, PRDX1 promotes NOXA ubiquitination and degradation, which completely depend on CUL5 neddylation. Further studies have demonstrated that PRDX1 oligomers bind with both the Nedd8-conjugating enzyme UBE2F and CUL5 and that this tricomplex is critical for CUL5 neddylation, since silencing PRDX1 or inhibiting PRDX1 oligomerization greatly dampens CUL5 neddylation and NOXA degradation. An increase in reactive oxygen species (ROS) is not only a hallmark of cancer cells but also the leading driving force for PRDX1 oligomerization. As shown in our study, although ROS play a role in upregulating NOXA mRNA transcription, ROS scavenging in CRC cells by N-acetyl-L-cysteine (NAC) can significantly reduce CUL5 neddylation and extend the NOXA protein half-life. Therefore, in CRC, PRDX1 plays a key role in maintaining intracellular homeostasis under conditions of high metabolic activity by reinforcing UBE2F-CUL5-mediated degradation of NOXA, which is also evidenced in the resistance of CRC cells to etoposide treatment. Based on these findings, targeting PRDX1 could be an effective strategy to overcome the resistance of CRC to DNA damage-inducing chemotherapeutics.
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- 2021
9. Cullin-5 neddylation-mediated NOXA degradation is enhanced by PRDX1 oligomers in colorectal cancer
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Jun Zhang, Guoli Li, Fengying Li, Jin Zeng, Yanzhong Wang, Jun Yang, Qingchao Tong, Xinyou Xie, Shoufang Xu, Jia Liu, Sining Fang, and Yilei Ma
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Cancer Research ,Programmed cell death ,biology ,Ubiquitylation ,Chemistry ,lcsh:Cytology ,Immunology ,Apoptosis ,Cell Biology ,Colorectal cancer ,Article ,Cell biology ,Cellular and Molecular Neuroscience ,Ubiquitin ,hemic and lymphatic diseases ,Cancer cell ,biology.protein ,Gene silencing ,Neddylation ,lcsh:QH573-671 ,Peroxiredoxin ,Cullin - Abstract
NOXA, a BH3-only proapoptotic protein involved in regulating cell death decisions, is highly expressed but short-lived in colorectal cancer (CRC). Neddylated cullin-5 (CUL5)-mediated ubiquitination and degradation of NOXA is crucial to prevent its overaccumulation and maintain an appropriate action time. However, how this process is manipulated by CRC cells commonly exposed to oxidative stress remain unknown. The peroxiredoxin PRDX1, a conceivable antioxidant overexpressed in CRC tissues, has been shown to inhibit apoptosis and TRAF6 ubiquitin-ligase activity. In this study, we found that PRDX1 inhibits CRC cell apoptosis by downregulating NOXA. Mechanistically, PRDX1 promotes NOXA ubiquitination and degradation, which completely depend on CUL5 neddylation. Further studies have demonstrated that PRDX1 oligomers bind with both the Nedd8-conjugating enzyme UBE2F and CUL5 and that this tricomplex is critical for CUL5 neddylation, since silencing PRDX1 or inhibiting PRDX1 oligomerization greatly dampens CUL5 neddylation and NOXA degradation. An increase in reactive oxygen species (ROS) is not only a hallmark of cancer cells but also the leading driving force for PRDX1 oligomerization. As shown in our study, although ROS play a role in upregulating NOXA mRNA transcription, ROS scavenging in CRC cells by N-acetyl-L-cysteine (NAC) can significantly reduce CUL5 neddylation and extend the NOXA protein half-life. Therefore, in CRC, PRDX1 plays a key role in maintaining intracellular homeostasis under conditions of high metabolic activity by reinforcing UBE2F-CUL5-mediated degradation of NOXA, which is also evidenced in the resistance of CRC cells to etoposide treatment. Based on these findings, targeting PRDX1 could be an effective strategy to overcome the resistance of CRC to DNA damage-inducing chemotherapeutics.
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- 2021
10. Novel thiazole-pyrazolone hybrids as potent ACE inhibitors and their cardioprotective effect on isoproterenol-induced myocardial infarction
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Xinyou Su, Guoying Su, and Hongwen You
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Male ,Pyrazolone ,Myocardial Infarction ,Pharmaceutical Science ,Angiotensin-Converting Enzyme Inhibitors ,Apoptosis ,Pharmacology ,medicine.disease_cause ,01 natural sciences ,Mitochondria, Heart ,Proinflammatory cytokine ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Downregulation and upregulation ,Western blot ,Drug Discovery ,medicine ,Animals ,Myocytes, Cardiac ,Pyrazolones ,Thiazole ,medicine.diagnostic_test ,010405 organic chemistry ,Chemistry ,Isoproterenol ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Disease Models, Animal ,Oxidative Stress ,Thiazoles ,Drug Design ,ACE inhibitor ,Cytokines ,Inflammation Mediators ,Apoptosis Regulatory Proteins ,Oxidative stress ,medicine.drug - Abstract
A facile synthesis of a group of novel thiazole-pyrazolone hybrids and their investigation for angiotensin-converting enzyme (ACE) inhibition are reported in this study. These compounds were synthesized using a well-known approach, based on the condensation of ethyl acetoacetate with thiazolylhydrazines, and characterized by various spectroscopic and analytical techniques. The entire set of compounds displayed a moderate-to-excellent inhibitory activity against ACE. In particular, compound 4i was found to be the most potent ACE inhibitor and was further studied for cardioprotective effects against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Compound 4i improved the cardiac function and prevented cardiac injury induced by ISO in Sprague Dawley rats. The levels of oxidative stress and proinflammatory cytokines were also restored to near normal by 4i as compared with the ISO group. In the Western blot analysis, compound 4i prevented mitochondrial apoptosis after MI by downregulating the expression of cleaved caspase-3 and Bax, with the upregulation of Bcl-2, as compared with the ISO group.
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- 2020
11. Low expression of RecQ‑like helicase 5 is associated with poor prognosis in patients with gastric cancer
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Xinyou Wang, Huashe Wang, Junsheng Peng, Yijia Lin, Honglei Chen, and Miao Li
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0301 basic medicine ,Cancer Research ,Messenger RNA ,Oncogene ,gastric cancer ,Cancer ,Articles ,Cell cycle ,Biology ,medicine.disease_cause ,medicine.disease ,Molecular medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,RecQ-like helicase 5 ,Apoptosis ,030220 oncology & carcinogenesis ,immunohistochemistry ,medicine ,Cancer research ,Immunohistochemistry ,prognosis ,Carcinogenesis - Abstract
The role of RecQ-like helicase 5 (RECQL5) in gastric cancer (GC) is unclear. This study investigated the expression, clinicopathological association and prognosis of RECQL5 protein in human GC. Firstly, the Oncomine database was used to determine the mRNA expression levels of RECQL5 in GC samples. GC samples and adjacent normal gastric tissue samples were subsequently assessed to determine RECQL5 protein expression levels using immunohistochemistry. The clinicopathological association with RECQL5 expression was analyzed. Multivariate Cox analysis was performed to determine the relationship between RECQL5 expression and survival outcomes. Data from the Oncomine database revealed that RECQL5 mRNA was significantly downregulated in GC tissues compared with that in normal gastric tissues (P
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- 2019
12. 2-Amino-4-(1-piperidine) pyridine exhibits inhibitory effect on colon cancer through suppression of FOXA2 expression
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Jieshu Wang, Bo Li, Kun Zhao, and Xinyou Su
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Chemistry ,Colorectal cancer ,Cell growth ,Cell ,Environmental Science (miscellaneous) ,medicine.disease ,Agricultural and Biological Sciences (miscellaneous) ,digestive system diseases ,Metastasis ,HT29 Cells ,medicine.anatomical_structure ,Apoptosis ,Cancer research ,medicine ,Large intestine ,Original Article ,Stem cell ,biological phenomena, cell phenomena, and immunity ,neoplasms ,Biotechnology - Abstract
The present study was aimed to investigate the effect of 2-amino-4-(1-piperidine) pyridine on migration and invasion of colon cancer cells. Treatment of colon cancer cells with 2-amino-4-(1-piperidine) pyridine reduced viability in concentration-based manner. The migration potential of HCT116 and HT29 cells was also suppressed on treatment with 2-amino-4-(1-piperidine) pyridine. In HCT116 and HT29 cells, apoptotic cell proportion was increased significantly by 2-amino-4-(1-piperidine) pyridine treatment. The expression of EMT and Vimentin in HCT116 and HT29 cells was reduced markedly on treatment with 2-amino-4-(1-piperidine) pyridine. The expression of E-cadherin was increased in HCT116 and HT29 cells by 2-amino-4-(1-piperidine) pyridine treatment. Treatment with 2-amino-4-(1-piperidine) pyridine reduced the expression of FOXA2 in HCT116 and HT29 cells. The 2-amino-4-(1-piperidine) pyridine treatment reduced growth of tumor in vivo in mice model. In summary, 2-amino-4-(1-piperidine) pyridine treatment inhibits colon cancer cell proliferation through down-regulation of FOXA2 expression. Therefore, 2-amino-4-(1-piperidine) pyridine can be used for the treatment of colon cancer.
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- 2019
13. Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin-induced cardio toxicity via suppressing oxidative stress and apoptosis
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Xinyou Su, Ping Wu, Luyan Zhang, Anurag Mishra, Lingling Zhang, and Nagaraja Sreeharsha
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0301 basic medicine ,Male ,medicine.medical_specialty ,Cardiotonic Agents ,Clinical Biochemistry ,Apoptosis ,Creatine ,medicine.disease_cause ,Biochemistry ,Cardiotoxins ,Rosiglitazone ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Lactate dehydrogenase ,Genetics ,medicine ,Animals ,Rats, Wistar ,Molecular Biology ,bcl-2-Associated X Protein ,chemistry.chemical_classification ,Glutathione peroxidase ,Myocardium ,Heart ,Cell Biology ,Glutathione ,Malondialdehyde ,Lipids ,PPAR gamma ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,chemistry ,Gene Expression Regulation ,Doxorubicin ,030220 oncology & carcinogenesis ,Toxicity ,Heme Oxygenase (Decyclizing) ,Oxidative stress ,medicine.drug - Abstract
We investigated the rosiglitazone (RSG) effect on adriamycin (ADM)-induced cardio toxicity in experimental animals. Forty adult Wistar male rats were separated into four groups as follows: normal control; RSG (10 mg/kg)-treated; ADM (10 mg/kg)-administered; and ADM (10 mg/kg) + RSG (10 mg/kg)-treated. Serum lipid level, different biochemical biomarkers, histological analysis, and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1), Caspase 3, B-cell lymphoma 2 (Bcl-2), and Bax gene expression were assessed in serum and cardiac tissue samples. Our results show that RSG treatment in ADM-administered animals significantly diminished low-density lipoprotein cholesterol, triglyceride, and total cholesterol, and increases high-density lipoprotein cholesterol (HDL-c) in comparison with the ADM group. RSG treatment reduced the effect of ADM administration on cardiac dysfunction markers such as cardiac troponin T Creatine Kinase-MB, aspartate aminotransferase, and lactate dehydrogenase, showing the amelioration of cardio toxicity in ADM-administered rats. Additionally, RSG treatment significantly decreased the level of malondialdehyde and nitric oxide in cardiovascular tissue. RSG-treated rats in combination with ADM likewise showed a significant increase in reduced glutathione, superoxide dismutase, catalase content, and the activity of glutathione peroxidase (GPx) as compared with ADM group. Moreover, RSG treatment in ADM rats significantly increased an Nrf2 and HO-1 expression in comparison with ADM group. While in apoptosis parameters, RSG treatment in ADM rats significantly diminished a cleaved caspase-3 and Bax expression as well as expanded Bcl-2 expression when contrasted with ADM group of rats. In conclusion, RSG is capable of protecting heart toxicity in ADM-treated animals through defensive effects on oxidative stress and biochemical markers.
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- 2019
14. Nicotinamide N-methyltransferase enhances resistance to 5-fluorouracil in colorectal cancer cells through inhibition of the ASK1-p38 MAPK pathway
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Yanwen Zhou, Xinyou Xie, Guiling Li, Huixing Liu, Xiuhong Wang, Fengying Li, Yanzhong Wang, Haitao Yu, Jun Zhang, and Zhi Ruan
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0301 basic medicine ,MAPK/ERK pathway ,MAP Kinase Signaling System ,p38 mitogen-activated protein kinases ,Mice, Nude ,Antineoplastic Agents ,colorectal cancer ,Nicotinamide N-methyltransferase ,Adenocarcinoma ,p38 MAPK ,MAP Kinase Kinase Kinase 5 ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,nicotinamide N-methyltransferase ,Cell Line, Tumor ,Animals ,Humans ,Medicine ,5-fluorouracil ,ASK1 ,1-methylnicotinamide ,Protein kinase A ,chemistry.chemical_classification ,Reactive oxygen species ,Nicotinamide ,business.industry ,Xenograft Model Antitumor Assays ,digestive system diseases ,030104 developmental biology ,Oncology ,chemistry ,Drug Resistance, Neoplasm ,Apoptosis ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Fluorouracil ,Colorectal Neoplasms ,business ,Research Paper - Abstract
Nicotinamide N-methyltransferase (NNMT), which converts nicotinamide to 1-methylnicotinamide (1-MNA), is overexpressed in a variety of human cancers and serves as a potential anti-cancer target. In this study, we investigated the effect of NNMT on 5-fluorouracil (5-FU) sensitivity of colorectal cancer (CRC) cells, and the underlying mechanisms. Our results show that down-regulation of NNMT in CRC HT-29 cells diminishes 5-FU resistance, while over expression of NNMT in SW480 cells enhances it. NNMT reduces reactive oxygen species (ROS) production induced by 5-FU by increasing 1-MNA in CRC cells. The reduction in ROS leads to inactivation of the ASK1-p38 mitogen-activated protein kinase (MAPK) pathway, which reduces 5-FU-induced apoptosis. In vivo, NNMT attenuates 5-FU-induced inhibition of CRC tumor growth in nude mice. These observations suggest that NNMT and the 1-MNA it produces inhibit the ASK1-p38 MAPK pathway, resulting in increased CRC cell resistance to 5-FU.
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- 2016
15. Decitabine shows potent anti-myeloma activity by depleting monocytic myeloid-derived suppressor cells in the myeloma microenvironment
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Hai-qing Lin, Guoqiang Li, Qi Shen, Lina Hu, Jihao Zhou, and Xinyou Zhang
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0301 basic medicine ,Male ,Cancer Research ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,T-Lymphocytes ,Decitabine ,Apoptosis ,Bone Marrow Cells ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,In vivo ,Internal medicine ,medicine ,Tumor Cells, Cultured ,Tumor Microenvironment ,Animals ,Multiple myeloma ,Cell Proliferation ,Mice, Inbred BALB C ,Hematology ,Chemistry ,Myeloid-Derived Suppressor Cells ,General Medicine ,medicine.disease ,Coculture Techniques ,Demethylating agent ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Myeloid-derived Suppressor Cell ,Bone marrow ,Multiple Myeloma ,medicine.drug - Abstract
Multiple myeloma (MM) remains incurable. The MM microenvironment supports MM cells’ survival and immune escape. Because myeloid-derived suppressor cells (MDSCs) is important in the MM microenvironment, and demethylating agent decitabine (DAC) can deplete MDSCs in vitro and in vivo, we hypothesized that DAC treatment could inhibit MM by depleting MDSCs in the MM microenvironment. In this study, we used the mouse IL6 secreting, myeloma cell line MPC11 as a model. MDSCs were sorted using magnetic beads and cultured. A transwell coculture assay was used to mimic the microenvironment in vitro. And MPC11-bearing mice model was used to observe the efficacy of DAC treatment in vivo. In vitro coculture assay indicated that MPC11 cells showed significantly lower proliferation rate, less IL6 production and more apoptosis when they were cocultured with bone marrow cells without MDSCs (nonMDSCs) or DAC-treated bone marrow cells (DAC BMs) than with MDSCs or PBS-treated bone marrow cells (CTR BM). Supplementation with M-MDSCs rescued the inhibitory effect of DAC BMs, while additional NOHA supplementation further antagonized the rescue effect of M-MDSCs. In MPC11-bearing mice, the combined treatment of DAC with anti-Gr1 antibody showed synergistic effect on inhibiting tumor growth and promoting T cell infiltration in the tumor tissue. M-MDSC reinfusion also antagonized the efficacy of DAC treatment. DAC treatment can inhibit myeloma cell proliferation and induce enhanced autologous T cell immune response by depleting M-MDSCs in the MM microenvironment. We believe that DAC treatment could improve the prognosis of MM in future.
- Published
- 2018
16. Overexpression of RECQL4 is associated with poor prognosis in patients with gastric cancer
- Author
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Xiaobin Wu, Xinyou Wang, Kaitao Yuan, Qiuning Wu, Junsheng Peng, Huashe Wang, and Honglei Chen
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Oncogene ,business.industry ,Lymphovascular invasion ,Cell ,Cancer ,Articles ,Cell cycle ,medicine.disease ,Gastroenterology ,Molecular medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Immunohistochemistry ,business - Abstract
The present study aimed to investigate the expression, clinical association, and prognosis of RecQ protein-like 4 (RECQL4) protein in human gastric cancers (GCs). The expression levels and prognostic value of RECQL4 were initially predicted by using bioinformatics. GC specimens and matched normal gastric tissues were evaluated by immunohistochemistry (IHC), and patient clinicopathological parameters and survival times were analyzed. Multivariate Cox analysis was used to determine the prognostic role of RECQL4 expression. The Oncomine database predicted that RECQL4 mRNA expression levels were significantly increased in GCs as compared with those in normal gastric tissues (P
- Published
- 2018
17. Butein suppresses hepatocellular carcinoma growth via modulating Aurora B kinase activity
- Author
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Tian Li, Xinyou Yu, Wei Li, Ting Liu, Yuanfeng Zhou, Wenbin Liu, Feng Gao, Li Zhou, and Ming Li
- Subjects
0301 basic medicine ,Cell cycle checkpoint ,Carcinoma, Hepatocellular ,Blotting, Western ,Aurora B kinase ,Administration, Oral ,Mice, Nude ,Apoptosis ,Applied Microbiology and Biotechnology ,Small hairpin RNA ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chalcones ,Cell Line, Tumor ,Animals ,Aurora Kinase B ,Humans ,Kinase activity ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Butein ,Cell growth ,Chemistry ,Kinase ,Cell Cycle ,Liver Neoplasms ,Cell Biology ,Cell Cycle Checkpoints ,Hep G2 Cells ,Flow Cytometry ,Immunohistochemistry ,digestive system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biological phenomena, cell phenomena, and immunity ,Developmental Biology ,Signal Transduction - Abstract
Aurora B is aberrantly expressed in various tumors and shown to be a promising target for cancer therapy. Butein, a chalcone isolated from Rhus cerniciflua, has demonstrated antitumor activities in different cancers. In this study, we aimed to validate whether Aurora B kinase was the direct target of butein to exhibit its potency in hepatocellular carcinoma (HCC). Comparing with the normal cell line and tissue, Aurora B was overexpressed in all tested HCC cells and the majority of tumor tissue. Knocking down of Aurora B with shRNA substantially inhibited HCC cell proliferation, colony formation and delayed tumor growth in nude mice. Except computer docking, a series of kinase assays revealed butein directly interacted with Aurora B and inhibited its kinase activity. Along with the decrease of Aurora B and histone H3 phosphorylation, HCC cells were induced G2/M cell cycle arrest and subjected to cell apoptosis. Butein-mediated antitumor activities were substantially impaired in Aurora B knockdown cells, suggesting Aurora B was an important target of butein in HCC. Oral administration of butein substantially restrained HCC xenograft growth and the expressions of Ki67 and phosphor-histone H3 were significantly decreased in butein-treated tissue. To the best of our knowledge, our studies revealed that Aurora B was the direct target of butein in HCC.
- Published
- 2018
18. Repression of Noxa by Bmi1 contributes to deguelin-induced apoptosis in non-small cell lung cancer cells
- Author
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Haidan Liu, Xinfang Yu, Xiaolong Ma, Zhenkun Xia, Huiling Zhou, Lijun Liu, Li Xie, Yifeng Yang, Jian Wang, Wei Li, and Xinyou Yu
- Subjects
0301 basic medicine ,Cell Survival ,macromolecular substances ,NSCLC ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,hemic and lymphatic diseases ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Rotenone ,Humans ,deguelin ,Mitogen-Activated Protein Kinase 7 ,Cell Proliferation ,Gene knockdown ,Noxa ,apoptosis ,Cell Biology ,Original Articles ,Bmi1 ,In vitro ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,chemistry ,Proto-Oncogene Proteins c-bcl-2 ,BMI1 ,Cell culture ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Original Article ,Deguelin ,Signal Transduction - Abstract
Deguelin, a natural rotenoid isolated from several plants, has been reported to exert anti‐tumour effects in various cancers. However, the molecular mechanism of this regulation remains to be fully elucidated. Here, we found that deguelin inhibited the growth of non‐small cell lung cancer (NSCLC) cells both in vitro and in vivo by downregulation of Bmi1 expression. Our data showed that Bmi1 is highly expressed in human NSCLC tissues and cell lines. Knockdown of Bmi1 significantly suppressed NSCLC cell proliferation and colony formation. Deguelin treatment attenuated the binding activity of Bmi1 to the Noxa promoter, thus resulting in Noxa transcription and apoptosis activation. Knockdown of Bmi1 promoted Noxa expression and enhanced deguelin‐induced apoptosis, whereas overexpression of Bmi1 down‐regulated Noxa protein level and deguelin‐induced apoptosis. Overall, our study demonstrated a novel apoptotic mechanism for deguelin to exert its anti‐tumour activity in NSCLC cells.
- Published
- 2017
19. Nicotinamide N-methyltransferase enhances the capacity of tumorigenesis associated with the promotion of cell cycle progression in human colorectal cancer cells
- Author
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Guiling Li, Jun Zhang, Zhi Ruan, Huixing Liu, Yanwen Zhou, Fengying Li, Xinyou Xie, Xiuhong Wang, Yanzhong Wang, and Haitao Yu
- Subjects
Male ,Colorectal cancer ,Biophysics ,Mice, Nude ,Apoptosis ,Endogeny ,Nicotinamide N-methyltransferase ,Biology ,medicine.disease_cause ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Mice ,Adenosine Triphosphate ,Cell Line, Tumor ,Nicotinamide N-Methyltransferase ,medicine ,Animals ,Humans ,Molecular Biology ,Mice, Inbred BALB C ,Cell growth ,Cell Cycle ,Cell cycle ,medicine.disease ,In vitro ,Neoplasm Proteins ,Cell biology ,Gene Expression Regulation, Neoplastic ,Female ,Colorectal Neoplasms ,Energy Metabolism ,Reactive Oxygen Species ,Carcinogenesis - Abstract
Nicotinamide N-methyltransferase (NNMT), an enzyme involved in the biotransformation and detoxification of many drugs and xenobiotic compounds, has been found to be overexpressed in several malignancies, including colorectal cancer. However, the biological function of NNMT and the related mechanisms in colorectal cancer have not been elucidated. In the present study, we investigated the effects of NNMT on tumorigenesis by overexpressing NNMT in the human colorectal cancer cells line SW480 which lacks constitutive NNMT expression, and downregulating NNMT expression in HT-29 cells, which exhibit high endogenous expression of NNMT. We found that NNMT significantly accelerates cell proliferation, enhances colony formation in vitro and tumorigenicity in mice; it also inhibits apoptosis, promotes cell cycle progression, increases ATP and 1-methylnicotinamide level and decreases ROS level. We also showed that 1-methylnicotinamide accelerates cell growth, inhibits apoptosis, promotes cell cycle progression, attenuates ROS production and increases ATP level. Our results indicate that NNMT enhances the capacity of tumorigenesis associated with the inhibition of cell apoptosis and the promotion of cell cycle progression in human colorectal cancer cells and the 1-methylnicotinamide increased by NNMT mediates the cellular effects of NNMT in cells. NNMT may play a vital role in energy balance and ROS induction.
- Published
- 2014
20. Demethylating agent decitabine disrupts tumor-induced immune tolerance by depleting myeloid-derived suppressor cells
- Author
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Jihao Zhou, Lina Hu, Guoqiang Li, Qi Shen, Yushi Yao, and Xinyou Zhang
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,T-Lymphocytes ,Decitabine ,Apoptosis ,Lymphocyte Activation ,Immune tolerance ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Immune system ,In vivo ,Cell Line, Tumor ,Neoplasms ,medicine ,Immune Tolerance ,Animals ,Humans ,Myeloid-Derived Suppressor Cells ,General Medicine ,Immunotherapy ,Mixed lymphocyte reaction ,Demethylating agent ,030104 developmental biology ,Oncology ,chemistry ,Immunology ,Myeloid-derived Suppressor Cell ,Azacitidine ,medicine.drug - Abstract
The immunoregulatory effect of demethylating agent decitabine (DAC) has been recognized recently. However, little is known about its impact on immune tolerance. In this study, we aimed to determine the impact of DAC on the immune tolerance induced by tumor cells. The effects of DAC on immune cells in vivo were measured by flow cytometry. Myeloid-derived suppressor cells (MDSCs) were sorted using magnetic beads and cultured in vitro. The mixed lymphocyte reaction was used to determine the immunoregulatory effect of DAC in vitro. An adoptive transfusion mouse model was established to evaluate the effect in vivo. We found that DAC treatment significantly depleted MDSCs in vivo by inducing MDSCs apoptosis. When given at a low dose, the immune effector cells were less affected by the treatment, except for MDSCs. The mixed lymphocyte reaction in vitro showed that T-cell responses were enhanced when MDSCs were depleted. Supplementation of MDSCs would attenuate this T-cell activation effect. Using an adoptive transfusion mouse model, we further demonstrated in vivo that DAC treatment could induce autologous anti-tumor immune response by depleting MDSCs. This study is the first to illustrate DAC’s immunoregulatory effect on immune tolerance. The disruption of immune tolerance is due to MDSCs depletion that induces an autologous immune response in vivo. By depleting MDSCs, DAC treatment removes one of the obstacles affecting anti-tumor immune activation and warrants further experimental and clinical studies to explore its potential utility in combination with various anti-tumor immunotherapies in the future.
- Published
- 2016
21. Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin‐induced cardio toxicity via suppressing oxidative stress and apoptosis.
- Author
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Zhang, Lingling, Wu, Ping, Zhang, Luyan, SreeHarsha, Nagaraja, Mishra, Anurag, and Su, Xinyou
- Subjects
PEROXISOME proliferator-activated receptors ,OXIDATIVE stress ,BLOOD lipids ,ANIMAL welfare ,LACTATE dehydrogenase ,GLUTATHIONE peroxidase ,ADIPOGENESIS - Abstract
We investigated the rosiglitazone (RSG) effect on adriamycin (ADM)‐induced cardio toxicity in experimental animals. Forty adult Wistar male rats were separated into four groups as follows: normal control; RSG (10 mg/kg)‐treated; ADM (10 mg/kg)‐administered; and ADM (10 mg/kg) + RSG (10 mg/kg)‐treated. Serum lipid level, different biochemical biomarkers, histological analysis, and nuclear factor erythroid 2‐related factor/heme oxygenase‐1 (Nrf2/HO‐1), Caspase 3, B‐cell lymphoma 2 (Bcl‐2), and Bax gene expression were assessed in serum and cardiac tissue samples. Our results show that RSG treatment in ADM‐administered animals significantly diminished low‐density lipoprotein cholesterol, triglyceride, and total cholesterol, and increases high‐density lipoprotein cholesterol (HDL‐c) in comparison with the ADM group. RSG treatment reduced the effect of ADM administration on cardiac dysfunction markers such as cardiac troponin T Creatine Kinase‐MB, aspartate aminotransferase, and lactate dehydrogenase, showing the amelioration of cardio toxicity in ADM‐administered rats. Additionally, RSG treatment significantly decreased the level of malondialdehyde and nitric oxide in cardiovascular tissue. RSG‐treated rats in combination with ADM likewise showed a significant increase in reduced glutathione, superoxide dismutase, catalase content, and the activity of glutathione peroxidase (GPx) as compared with ADM group. Moreover, RSG treatment in ADM rats significantly increased an Nrf2 and HO‐1 expression in comparison with ADM group. While in apoptosis parameters, RSG treatment in ADM rats significantly diminished a cleaved caspase‐3 and Bax expression as well as expanded Bcl‐2 expression when contrasted with ADM group of rats. In conclusion, RSG is capable of protecting heart toxicity in ADM‐treated animals through defensive effects on oxidative stress and biochemical markers. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
22. Repression of Noxa by Bmi1 contributes to deguelin‐induced apoptosis in non‐small cell lung cancer cells.
- Author
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Li, Wei, Yu, Xinfang, Xia, Zhenkun, Yu, Xinyou, Xie, Li, Ma, Xiaolong, Zhou, Huiling, Liu, Lijun, Wang, Jian, Yang, Yifeng, and Liu, Haidan
- Subjects
NON-small-cell lung carcinoma ,APOPTOSIS ,ROTENOIDS ,CELL proliferation ,DOWNREGULATION - Abstract
Deguelin, a natural rotenoid isolated from several plants, has been reported to exert anti‐tumour effects in various cancers. However, the molecular mechanism of this regulation remains to be fully elucidated. Here, we found that deguelin inhibited the growth of non‐small cell lung cancer (NSCLC) cells both in vitro and in vivo by downregulation of Bmi1 expression. Our data showed that Bmi1 is highly expressed in human NSCLC tissues and cell lines. Knockdown of Bmi1 significantly suppressed NSCLC cell proliferation and colony formation. Deguelin treatment attenuated the binding activity of Bmi1 to the Noxa promoter, thus resulting in Noxa transcription and apoptosis activation. Knockdown of Bmi1 promoted Noxa expression and enhanced deguelin‐induced apoptosis, whereas overexpression of Bmi1 down‐regulated Noxa protein level and deguelin‐induced apoptosis. Overall, our study demonstrated a novel apoptotic mechanism for deguelin to exert its anti‐tumour activity in NSCLC cells. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
23. Down-regulation of nicotinamide N-methyltransferase induces apoptosis in human breast cancer cells via the mitochondria-mediated pathway
- Author
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Haitao Yu, Guiling Li, Jun Zhang, Xinyou Xie, and Yanzhong Wang
- Subjects
Enzyme Metabolism ,Cancer Treatment ,Tetrazolium Salts ,lcsh:Medicine ,Apoptosis ,Mitochondrion ,Biochemistry ,Small hairpin RNA ,Oxidative Damage ,Mice ,Drug Discovery ,Molecular Cell Biology ,Basic Cancer Research ,Breast Tumors ,Nicotinamide N-Methyltransferase ,RNA, Small Interfering ,lcsh:Science ,Clinical Chemistry ,Multidisciplinary ,Cell Death ,Cytochromes c ,Gene Therapy ,Flow Cytometry ,Clinical Laboratory Sciences ,Enzymes ,Mitochondria ,Gene Expression Regulation, Neoplastic ,Oncology ,Medicine ,Oncology Agents ,Female ,RNA Interference ,Research Article ,Blotting, Western ,Nicotinamide N-methyltransferase ,Breast Neoplasms ,Biology ,Real-Time Polymerase Chain Reaction ,Cell Growth ,Diagnostic Medicine ,Cell Line, Tumor ,Genetics ,Cancer Genetics ,Cancer Detection and Diagnosis ,Early Detection ,Animals ,Humans ,Protein kinase B ,DNA Primers ,Cell growth ,lcsh:R ,Cancers and Neoplasms ,Chemotherapy and Drug Treatment ,Thiazoles ,Cell culture ,Cancer cell ,Cancer research ,lcsh:Q ,Gene Function ,Reactive Oxygen Species - Abstract
Nicotinamide N-methyltransferase (NNMT) has been found involved in cell proliferation of several malignancies. However, the functional role of NNMT in breast cancer has not been elucidated. In the present study, we showed that NNMT was selectively expressed in some breast cancer cell lines, down-regulation of NNMT expression in Bcap-37 and MDA-MB-231 cell lines by NNMT shRNA significantly inhibited cell growth in vitro, decreased tumorigenicity in mice and induced apoptosis. The silencing reciprocal effect of NNMT was confirmed by over-expressing NNMT in the MCF-7 and SK-BR-3 breast cancer cell lines which lack constitutive expression of NNMT. In addition, down-regulation of NNMT expression resulted in reducing expression of Bcl-2 and Bcl-xL, up-regulation of Bax, Puma, cleaved caspase-9, cleaved caspase-3 and cleaved PARP, increasing reactive oxygen species production and release of cytochrome c from mitochondria, and decreasing the phosphorylation of Akt and ERK1/2. These data suggest that down-regulation of NNMT induces apoptosis via the mitochondria-mediated pathway in breast cancer cells.
- Published
- 2014
24. Physiological basis of genetic variation in leaf photosynthesis among rice (Oryza sativa L.) introgression lines under drought and well-watered conditions
- Author
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Tjeerd Jan Stomph, Huaqi Wang, Paul C. Struik, Xinyou Yin, and Junfei Gu
- Subjects
Methyltransferase ,chlorophyll fluorescence measurements ,5-bisphosphate carboxylase ,Physiology ,Quantitative Trait Loci ,ribulose-1 ,mesophyll conductance ,Plant Science ,drought ,Biology ,internal conductance ,Models, Biological ,modelling ,co2 diffusion ,Genetic variation ,Botany ,Oryza sativa L ,Epigenetics ,Leerstoelgroep Gewas- en onkruidecologie ,Oryza sativa ,photosynthesis ,c-3 plants ,combined gas-exchange ,rice ,ribulose-1,5-bisphosphate carboxylase ,food and beverages ,Genetic Variation ,use efficiency ,Oryza ,Plant Transpiration ,Methylation ,Carbon Dioxide ,PE&RC ,Chromatin ,Cell biology ,Plant Leaves ,transpiration efficiency ,Apoptosis ,stomatal conductance ,DNA methylation ,Sunlight ,Crop and Weed Ecology ,carbon-isotope discrimination ,Research Paper - Abstract
To understand the physiological basis of genetic variation and resulting quantitative trait loci (QTLs) for photosynthesis in a rice (Oryza sativa L.) introgression line population, 13 lines were studied under drought and well-watered conditions, at flowering and grain filling. Simultaneous gas exchange and chlorophyll fluorescence measurements were conducted at various levels of incident irradiance and ambient CO(2) to estimate parameters of a model that dissects photosynthesis into stomatal conductance (g(s)), mesophyll conductance (g(m)), electron transport capacity (J(max)), and Rubisco carboxylation capacity (V(cmax)). Significant genetic variation in these parameters was found, although drought and leaf age accounted for larger proportions of the total variation. Genetic variation in light-saturated photosynthesis and transpiration efficiency (TE) were mainly associated with variation in g(s) and g(m). One previously mapped major QTL of photosynthesis was associated with variation in g(s) and g(m), but also in J(max) and V(cmax) at flowering. Thus, g(s) and g(m), which were demonstrated in the literature to be responsible for environmental variation in photosynthesis, were found also to be associated with genetic variation in photosynthesis. Furthermore, relationships between these parameters and leaf nitrogen or dry matter per unit area, which were previously found across environmental treatments, were shown to be valid for variation across genotypes. Finally, the extent to which photosynthesis rate and TE can be improved was evaluated. Virtual ideotypes were estimated to have 17.0% higher photosynthesis and 25.1% higher TE compared with the best genotype investigated. This analysis using introgression lines highlights possibilities of improving both photosynthesis and TE within the same genetic background.
- Published
- 2012
25. Nicotinamide N-methyltransferase enhances the capacity of tumorigenesis associated with the promotion of cell cycle progression in human colorectal cancer cells.
- Author
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Xie, Xinyou, Yu, Haitao, Wang, Yanzhong, Zhou, Yanwen, Li, Guiling, Ruan, Zhi, Li, Fengying, Wang, Xiuhong, Liu, Huixing, and Zhang, Jun
- Subjects
- *
NICOTINAMIDE , *METHYLTRANSFERASES , *NEOPLASTIC cell transformation , *CANCER cells , *COLON cancer , *CANCER invasiveness , *DETOXIFICATION (Alternative medicine) - Abstract
Nicotinamide N-methyltransferase (NNMT), an enzyme involved in the biotransformation and detoxification of many drugs and xenobiotic compounds, has been found to be overexpressed in several malignancies, including colorectal cancer. However, the biological function of NNMT and the related mechanisms in colorectal cancer have not been elucidated. In the present study, we investigated the effects of NNMT on tumorigenesis by overexpressing NNMT in the human colorectal cancer cells line SW480 which lacks constitutive NNMT expression, and downregulating NNMT expression in HT-29 cells, which exhibit high endogenous expression of NNMT. We found that NNMT significantly accelerates cell proliferation, enhances colony formation in vitro and tumorigenicity in mice; it also inhibits apoptosis, promotes cell cycle progression, increases ATP and 1-methylnicotinamide level and decreases ROS level. We also showed that 1-methylnicotinamide accelerates cell growth, inhibits apoptosis, promotes cell cycle progression, attenuates ROS production and increases ATP level. Our results indicate that NNMT enhances the capacity of tumorigenesis associated with the inhibition of cell apoptosis and the promotion of cell cycle progression in human colorectal cancer cells and the 1-methylnicotinamide increased by NNMT mediates the cellular effects of NNMT in cells. NNMT may play a vital role in energy balance and ROS induction. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
26. LAG3 and PD1 Regulate CD8+ T Cell in Diffuse Large B-cell Lymphoma Patients.
- Author
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Liu, Ying, Guo, Xinhong, Zhan, Lingbo, Wang, Lei, Wang, Xinyou, and Jiang, Ming
- Subjects
- *
DIFFUSE large B-cell lymphomas , *T cells , *CELL death , *IMMUNE checkpoint proteins , *THERAPEUTICS , *APOPTOSIS , *TRANSCRANIAL magnetic stimulation - Abstract
Background. Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous lymphoid malignancy. The unsatisfactory outcome for refractory patients has prompted efforts to explore new therapeutic approaches for DLBCL. However, the mechanisms involved in treatment associated with immune checkpoints remain unclear. This study is aimed at investigating the potential roles of programmed cell death protein 1 (PD1) and lymphocyte activation gene 3 (LAG3) in CD8+ T cells for treatment in DLBCL. Methods. Utilizing flow cytometry, we examined the content of T cells, the levels of cytokines, and the expression of PD1 and LAG3 in patients with DLBCL as well as in healthy controls. Levels of cytokines in CD8+ T cells from DLBCL patients before and after treatment were compared by blocking of PD1 and LAG3 in magnetic bead-sorted CD8+ T cells. Results. We found that the proportion of CD4+ T cells and CD8+ T cells was increased in DLBCL patients after treatment. The levels of cytokines trended toward those of healthy controls in treatment. PD1 (+), LAG3 (+), or PD1 (+) LAG3 (+) were all expressed in lower amounts in CD4+ T cells and CD8+ T cells after treatment than in untreated DLBCL patients. In addition, blockade of PD1 and LAG3 in sorted CD8+ T cells markedly inhibited cytokine production in response to treatment. Conclusion. PD1 and LAG3 in CD8+ T cells may be important targets of therapy and play therapeutic role in patients with DLBCL. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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