共查询到20条相似文献，搜索用时 31 毫秒
1.
Arunachalam Kalaiarasi Renu Sankar Chidambaram Anusha Kandasamy Saravanan Kalyanasundaram Aarthy Selvaraj Karthic Theodore lemuel Mathuram Vilwanathan Ravikumar 《Biotechnology letters》2018,40(2):249-256
Objectives
Copper oxide nanoparticles (CuO NPs) promoting anticancer activity may be due to the regulation of various classes of histone deacetylases (HDACs).Results
Green-synthesized CuO NPs significantly arrested total HDAC level and also suppressed class I, II and IV HDACs mRNA expression in A549 cells. A549 cells treated with CuO NPs downregulated oncogenes and upregulated tumor suppressor protein expression. CuO NPs positively regulated both mitochondrial and death receptor-mediated apoptosis caspase cascade pathway in A549 cells.Conclusion
Green-synthesized CuO NPs inhibited HDAC and therefore shown apoptosis mediated anticancer activity in A549 lung cancer cell line.2.
RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
María Fernanda Rubio María Cecilia Lira Francisco Damián Rosa Adrían Dario Sambresqui María Cecilia Salazar Güemes Mónica Alejandra Costas 《Cancer cell international》2017,17(1):111
Background
RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition of apoptosis and autophagy. Both mechanisms are involved in resistance to treatment with chemotherapeutic agents. The aim of this study was to investigate its role in chemoresistance of colorectal cancer.Methods
The sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells HT-29, HCT 116 and Lovo cell lines, expressing high or low natural levels of RAC3, was investigated using viability assays.Results
In HCT 116 cells, we found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy was strongly induced, while oxaliplatin has shown a similar ability to induce both of them. However, in HCT 116 cells expressing a short hairpin RNA for RAC3, we found an increased sensitivity to both drugs if it is compared with control cells. 5-Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent apoptosis and produce an increase of autophagy. In addition, both process have shown to be trigged faster than in control cells, starting earlier after stimulation.Conclusions
Our results suggest that RAC3 expression levels influence the sensitivity to chemotherapeutic drugs. Therefore, the knowledge of RAC3 expression levels in tumoral samples could be an important contribution to design new improved therapeutic strategies in the future.3.
Background
Rhodopsin mutations are associated with the autosomal dominant form of retinitis pigmentosa. T17M mutation in rhodopsin predisposes cells to endoplasmic reticulum (ER) stress and induces cell death. This study aimed to examine whether chemical chaperone 4-phenylbutyrate prevents ER stress induced by rhodopsin T17M.Results
ARPE-19 cells were transfected with myc-tagged wild-type (WT) and T17M rhodopsin constructs. Turnover of WT and T17M rhodopsin was measured by cycloheximide chase analysis. The activity of ubiquitin-proteasome system was evaluated by GFPU reporter. We found that T17M rhodopsin was misfolded, ubiqutinated and eliminated by ER-associated degradation pathway (ERAD) in ARPE-19 cells. Accumulated T17M rhodopsin induced unfolded protein response, but had no effect on the activity of ubiquitin proteasome system. Moreover, chemical chaperone 4-phenylbutyrate facilitated the turnover of T17M rhodopsin and prevented apoptosis and ER stress induced by T17M rhodopsin.Conclusions
Chemical chaperone could attenuate UPR signaling and ER stress induced by T17M rhodopsin and has potential therapeutic significance for retinitis pigmentosa.4.
Chuanfu Zhang Yutao Yang Xiaowei Zhou Zhixin Yang Xuelin Liu Zhiliang Cao Hongbin Song Yuxian He Peitang Huang 《Virology journal》2011,8(1):181
Background
Our previous study showed that the NS1 protein of highly pathogenic avian influenza A virus H5N1 induced caspase-dependent apoptosis in human alveolar basal epithelial cells (A549), supporting its function as a proapoptotic factor during viral infection, but the mechanism is still unknown.Results
To characterize the mechanism of NS1-induced apoptosis, we used a two-hybrid system to isolate the potential NS1-interacting partners in A549 cells. We found that heat shock protein 90 (Hsp90) was able to interact with the NS1 proteins derived from both H5N1 and H3N2 viruses, which was verified by co-immunoprecitation assays. Significantly, the NS1 expression in the A549 cells dramatically weakened the interaction between Apaf-1 and Hsp90 but enhanced its interaction with cytochrome c (Cyt c), suggesting that the competitive binding of NS1 to Hsp90 might promote the Apaf-1 to associate with Cyt c and thus facilitate the activation of caspase 9 and caspase 3.Conclusions
The present results demonstrate that NS1 protein of Influenza A Virus interacts with heat hock protein Hsp90 and meidates the apoptosis induced by influenza A virus through the caspase cascade.5.
Jian Ge Qianxue Chen Baohui Liu Long Wang Shenqi Zhang Baowei Ji 《Cellular & molecular biology letters》2017,22(1):30
Background
Gliomas are commonly malignant tumors that arise in the human central nervous system and have a low overall five-year survival rate. Previous studies reported that several members of Rab GTPase family are involved in the development of glioma, and abnormal expression of Rab small GTPases is known to cause aberrant tumor cell behavior. In this study, we characterized the roles of Rab21 (Rab GTPase 21), a member of Rab GTPase family, in glioma cells.Methods
The study involved downregulation of Rab21 in two glioma cell lines (T98G and U87) through transfection with specific-siRNA. Experiments using the MTT assay, cell cycle analysis, apoptosis assay, real-time PCR and western blot were performed to establish the expression levels of related genes.Results
The results show that downregulation of Rab21 can significantly inhibit cell growth and remarkably induce cell apoptosis in T98G and U87 cell lines. Silencing Rab21 resulted in significantly increased expression of apoptosis-related proteins (caspase7, Bim and Bax) in glioma cells.Conclusions
We inferred that Rab21 silencing can induce apoptosis and inhibit proliferation in human glioma cells, indicating that Rab21 might act as an oncogene and serve as a novel target for glioma therapy.6.
Background
Estrogen improves cardiac recovery after ischemia/reperfusion (I/R) by yet incompletely understood mechanisms. Mitochondria play a crucial role in I/R injury through cytochrome c-dependent apoptosis activation. We tested the hypothesis that 17β-estradiol (E2) as well as a specific ERβ agonist improve cardiac recovery through estrogen receptor (ER)β-mediated mechanisms by reducing mitochondria-induced apoptosis and preserving mitochondrial integrity.Methods
We randomized ovariectomized C57BL/6N mice 24h before I/R to pre-treatment with E2 or a specific ERβ agonist (ERβA). Isolated hearts were perfused for 20min prior to 30min global ischemia followed by 40min reperfusion.Results
Compared with controls, ERβA and E2 treated groups showed a significant improvement in cardiac recovery, i.e. an increase in left ventricular developed pressure, dP/dtmax and dP/dtmin. ERβA and E2 pre-treatment led to a significant reduction in apoptosis with decreased cytochrome c release from the mitochondria and increased mitochondrial levels of anti-apoptotic Bcl2 and ACAA2. Protein levels of mitochondrial translocase inner membrane (TIM23) and mitochondrial complex I of respiratory chain were increased by ERβA and E2 pre-treatment. Furthermore, we found a significant increase of myosin light chain 2 (MLC2) phosphorylation together with ERK1/2 activation in E2, but not in ERβA treated groups.Conclusions
Activation of ERβ is essential for the improvement of cardiac recovery after I/R through the inhibition of apoptosis and preservation of mitochondrial integrity and can be a achieved by a specific ERβ agonist. Furthermore, E2 modulates MLC2 activation after I/R independent of ERβ.7.
Mona Pourjafar Massoud Saidijam Katayoon Etemadi Rezvan Najafi 《Biotechnology letters》2017,39(8):1263-1268
Objectives
To investigate the effect of all-trans retinoic acid (ATRA) on caspase 3 activity, matrix metalloproteinase 2 (MMP-2), and MMP-9 expression and activity as well as in vitro rat bone marrow-derived mesenchymal stem cells (MSCs) migration.Results
The expression of the MMP-2/-9 was at least five times higher in ATRA-treated MSCs (P < 0.001), and MMP-2/-9 activity was enhanced with increasing doses compared to the control MSCs. The caspase three activity was attenuated by ATRA preconditioning. Scratch test showed that ATRA could promote the migration capacity of the MSCs compared to the untreated MSCs in a dose-dependent manner.Conclusion
ATRA increases the in vitro migration capacity of the MSCs through stimulating the expression and activity of MMP-2/-9 and inhibiting caspase three enzyme activity.8.
Objectives
To investigate the biological functions of microRNA-144-3p with respect to proliferation and apoptosis of human salivary adenoid carcinoma cell lines via mTOR.Results
After transfection of microRNA-144-3p agomir, cell viability assays confirmed that the salivary adenoid carcinoma cell (SACC) proliferation was inhibited and apoptosis was induced. Dual luciferase reporter assay validated that the mammalian target of rapamycin (mTOR) was a direct target of miR-144-3p. Western blot, immunofluorescent analysis and a xenograft mouse model of adenoid cystic carcinoma indicated that miR-144-3p was a tumor suppressor and repressed mTOR expression and signaling in SACCs.Conclusions
MicroRNA-144-3p inhibits proliferation and induces apoptosis of human salivary adenoid carcinoma cells by downregulating mTOR expression in vitro and in vivo.9.
Guoquan Wang Xiao Wang Xiaoping Huang Huiyong Yang Suqiu Pang Xiaolan Xie Shulan Zeng Junsheng Lin Yong Diao 《Cancer cell international》2015,16(1):90
Background
Kallistatin is a serine proteinase inhibitor and heparin-binding protein. It is considered an endogenous angiogenic inhibitor. In addition, multiple studies demonstrated that kallistatin directly inhibits cancer cell growth. However, the molecular mechanisms underlying these effects remain unclear.Methods
Pull-down, immunoprecipitation, and immunoblotting were used for binding experiments. To elucidate the mechanisms, integrin β3 knockdown (siRNA) or blockage (antibody treatment) on the cell surface of small the cell lung cancer NCI-H446 cell line was used.Results
Interestingly, kallistatin was capable of binding integrin β3 on the cell surface of NCI-H446 cells. Meanwhile, integrin β3 knockdown or blockage resulted in loss of antitumor activities induced by kallistatin. Furthermore, kallistatin suppressed tyrosine phosphorylation of integrin β3 and its downstream signaling pathways, including FAK/-Src, AKT and Erk/MAPK. Viability, proliferation and migration of NCI-H446 cells were inhibited by kallistatin, with Bcl-2 and Grb2 downregulation, and Bax, cleaved caspase-9 and caspase 3 upregulation.Conclusions
These findings reveal a novel role for kallistatin in preventing small cell lung cancer growth and mobility, by direct interaction with integrin β3, leading to blockade of the related signaling pathway.10.
Faisal?Thayyullathil Siraj?Pallichankandy Anees?Rahman Jaleel?Kizhakkayil Shahanas?Chathoth Mahendra?Patel Sehamuddin?Galadari
Background
Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that selectively activates and induces apoptosis in cancer cells, but not in normal cells. The cancer specific pro-apoptotic function of Par-4 is encoded in its centrally located SAC (Selective for Apoptosis induction in Cancer cells) domain (amino acids 137–195). The SAC domain itself is capable of nuclear entry, caspase activation, inhibition of NF-κB activity, and induction of apoptosis in cancer cells. However, the precise mechanism(s) of how the SAC domain is released from Par-4, in response to apoptotic stimulation, is not well explored.Results
In this study, we demonstrate for the first time that sphingosine (SPH), a member of the sphingolipid family, induces caspase-dependant cleavage of Par-4, leading to the release of SAC domain containing fragment from it. Par-4 is cleaved at the EEPD131G site on incubation with caspase-3 in vitro, and by treating cells with several anti-cancer agents. The caspase-3 mediated cleavage of Par-4 is blocked by addition of the pan-caspase inhibitor z-VAD-fmk, caspase-3 specific inhibitor Ac-DEVD-CHO, and by introduction of alanine substitution for D131 residue. Moreover, suppression of SPH-induced Akt dephosphorylation also abrogated the caspase dependant cleavage of Par-4.Conclusion
Evidence provided here shows that Par-4 is cleaved by caspase-3 during SPH-induced apoptosis. Cleavage of Par-4 leads to the generation of SAC domain containing fragment which may possibly be essential and sufficient to induce or augment apoptosis in cancer cells.11.
Tao Wang Ning Yu Miao Qian Jie Feng Shuyang Cao Jun Yin Quan Zhang 《Cancer cell international》2018,18(1):200
Background
Apoptosis and autophagy are known to play important roles in cancer development. It has been reported that HVJ-E induces apoptosis in cancer cells, thereby inhibiting the development of tumors. To define the mechanism by which HVJ-E induces cell death, we examined whether HVJ-E activates autophagic and apoptotic signaling pathways in HeLa cells.Methods
Cells were treated with chloroquine (CQ) and rapamycin to determine whether autophagy is involved in HVJ-E-induced apoptosis. Treatment with the ERK inhibitor, U0126, was used to determine whether autophagy and apoptosis are mediated by the ERK pathway. Activators of the PI3K/Akt/mTOR/p70S6K pathway, 740 Y-P and SC79, were used to characterize its role in HVJ-E-induced autophagy. siRNA against Atg3 was used to knock down the protein and determine whether it plays a role in HVJ-E-induced apoptosis in HeLa cells.Results
We found that HVJ-E infection inhibited cell viability and induced apoptosis through the mitochondrial pathway, as evidenced by the expression of caspase proteins. This process was promoted by rapamycin treatment and inhibited by CQ treatment. HVJ-E-induced autophagy was further blocked by 740 Y-P, SC79, and U0126, indicating that both the ERK- and the PI3K/Akt/mTOR/p70S6K-pathways were involved. Finally, autophagy-mediated apoptosis induced by HVJ-E was inhibited by siRNA-mediated Atg3 knockdown.Conclusion
In HeLa cells, HVJ-E infection triggered autophagy through the PI3K/Akt/mTOR/p70S6K pathway in an ERK1/2-dependent manner, and the induction of autophagy promoted apoptosis in an Atg3-dependent manner.12.
Background
Mycobacterium smegmatis, a rapidly growing non-tuberculosis mycobacterium, is a good model for studying the pathogenesis of tuberculosis because of its genetic similarity to Mycobacterium tuberculosis (Mtb). Macrophages remove mycobacteria during an infection. Macrophage apoptosis is a host defense mechanism against intracellular bacteria. We have reported that endoplasmic reticulum (ER) stress is an important host defense mechanism against Mtb infection.Results
In this study, we found that M. smegmatis induced strong ER stress. M. smegmatis-induced reactive oxygen species (ROS) play a critical role in the induction of ER stress-mediated apoptosis. Pretreatment with an ROS scavenger suppressed M. smegmatis-induced ER stress. Elimination of ROS decreased the ER stress response and significantly increased the intracellular survival of M. smegmatis. Interestingly, inhibition of phagocytosis significantly decreased ROS synthesis, ER stress response induction, and cytokine production.Conclusions
Phagocytosis of M. smegmatis induces ROS production, leading to production of proinflammatory cytokines. Phagocytosis-induced ROS is associated with the M. smegmatis-mediated ER stress response in macrophages. Therefore, phagocytosis plays a critical role in the induction of ER stress-mediated apoptosis during mycobacterial infection.13.
14.
15.
Yan Zhang Xia Meng Cheng Li Zhoulin Tan Xinwei Guo Zhiting Zhang Tao Xi 《Biotechnology letters》2017,39(7):959-966
Objectives
To demonstrate that miR-9 inhibits autophagy by down-regulating Beclin1 and thus enhances the sensitivity of A549 cells to cisplatin.Results
MiR-9 inhibited Beclin1 expression by binding to its 3′UTR. The inhibition decreased the cisplatin-induced autophagy in A549 cells, evidenced by the decreased expression of LC3II and GFP-LC3 puncta and the increased expression of P62. Upregulation of miR-9 level enhanced the sensibility of A549 cells to cisplatin and increased the cisplatin-induced apoptosis. Overexpression of Beclin1 reversed above effects of miR-9 mimics, cisplatin-induced autophagy was increased and apoptosis was decreased.Conclusions
MiR-9 inhibits autophagy via targeting Beclin1 3′UTR and thus enhances cisplatin sensitivity in A549 cells.16.
17.
Laleh Shariati Mehran Modaress Hossein Khanahmad Zahra Hejazi Mohammad Amin Tabatabaiefar Mansoor Salehi Mohammad Hossein Modarressi 《Biotechnology letters》2016,38(8):1243-1250
Objective
To compare methods for erythroid differentiation of K562 cells that will be promising in the treatment of beta-thalassemia by inducing γ-globin synthesis.Results
Cells were treated separately with: RPMI 1640 medium without glutamine, RPMI 1640 medium without glutamine supplemented with 1 mM sodium butyrate, RPMI 1640 medium supplemented with 1 mM sodium butyrate, 25 µg cisplatin/ml, 0.1 µg cytosine arabinoside/ml. The highest differentiation (84 %) with minimum toxicity was obtained with cisplatin at 15 µg /ml. Real-time RT-PCR showed that expression of the γ-globin gene was significantly higher in the cells differentiated with cisplatin compared to undifferentiated cells (P < 0.001).Conclusions
Cisplatin is useful in the experimental therapy of ß-globin gene defects and can be considered for examining the basic mechanism of γ-reactivation.18.
Background
The adhesion of Plasmodium falciparum parasitized red blood cell (PRBC) to human endothelial cells (EC) induces inflammatory processes, coagulation cascades, oxidative stress and apoptosis. These pathological processes are suspected to be responsible for the blood-brain-barrier and other organs' endothelial dysfunctions observed in fatal cases of malaria. Atorvastatin, a drug that belongs to the lowering cholesterol molecule family of statins, has been shown to ameliorate endothelial functions and is widely used in patients with cardiovascular disorders.Methods
The effect of this compound on PRBC induced endothelial impairments was assessed using endothelial co-culture models.Results
Atorvastatin pre-treatment of EC was found to reduce the expression of adhesion molecules and P. falciparum cytoadherence, to protect cells against PRBC-induced apoptosis and to enhance endothelial monolayer integrity during co-incubation with parasites.Conclusions
These results might suggest a potential interest use of atorvastatin as a protective treatment to interfere with the pathophysiological cascades leading to severe malaria.19.
W Al Sarakbi M Salhab V Thomas K Mokbel 《International Seminars in Surgical Oncology : ISSO》2005,2(1):15
Background
The objective of this study was to determine the concordance rate between core needle biopsy (CNB) and surgical excision of invasive breast cancer regarding the oestrogen receptor (ER) and Progesterone receptor (PgR) status as determined by Immunohistochemistry (IHC).Methods
Hormone receptor status was established using IHC (using quickscore system 0–8) on preoperative CNB and subsequent surgical excision in 93 patients with invasive breast cancer. Results were compared taking into account tumour's size, grade, and patient's age.Results
The ER concordance rate between CNB and surgical excisions was 95%. The PgR concordance rate was 89%. This shows that CNB has a sensitivity of 97% for ER and 95% for PgR.There is a positive correlation of ER and PgR between CNB and surgical excision (p < 0.000001). There was no significant difference in the number of core biopsies between concordant and discordant cases.Conclusion
Preoperative core biopsy is highly sensitive for the IHC detection of ER and PgR in invasive breast cancer. The concordance rate is higher for ER than PgR, which could be due to the fact that ER is more homogeneously distributed.20.