Celecoxib Attenuates Cartilage Matrix Damage in Arthritis Rats by Inhibiting NF-κ B

2020 ◽  
Vol 10 (4) ◽  
pp. 531-537
Author(s):  
Lukuan Du ◽  
Zhenghui Jiang ◽  
Zhaohui Wang ◽  
Liming Wang
Keyword(s):  
Caspase 3 ◽  
Sham Group ◽  
Culture Supernatant ◽  
Cartilage Tissue ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Protein Expressions ◽  
Col2a1 Expression ◽  
Matrix Damage

Objective: Celecoxib selectively inhibits the activity of COX-2 and the production of prostaglandin (PG), and plays a therapeutic role in treating osteoarthritis (OA). NF-κB signaling and IL-1α and TNFα are involved in OA pathogenesis. This study explored whether Celecoxib might exert therapeutic effects on OA through regulating NF-κB signaling and IL-1β and TNF release in OA rat model. Method : The contents of MMP-13, Hyp, IL-1β and TNFα in synovial fluid were detected by ELISA. The protein expressions of NF-κ B p-p65, COL2A1 and the activity of caspase-3 were detected. OA model rats were separated into OA group and OA+ Celecoxib group followed by analysis of MMP-13, Hyp, IL-1β and TNF level in articular fluid by ELISA and p-p65 and COL2A1 level and caspase-3 activity by western blot. Rat cartilage tissue was cultured and divided into control group, LPS group and LPS+ Celecoxib group followed by analysis of expressions of p-p65 and COL2A1 in cartilage tissue, IL-1 and TNF content in culture supernatant, and chondrocyte apoptosis. Results: Compared with Sham group, p-p65 expression and caspase-3 activity in cartilage tissue of OA rats was increased and COL2A1 level was reduced. Meanwhile the expression of MMP-13, Hyp, IL-1β and TNF in articular fluid of OA rats was increased. Compared to OA group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in OA+ Celecoxib treatment group along with decreased MMP-13, Hyp, IL-1β and TNF level in articular fluid. p-p65 expression and caspase-3 activity in LPS group was increased and COL2A1 expression was decreased with increased IL-beta; and TNF content. Compared to LPS group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in LPS+ Celecoxib group with decreased content of IL-1β and TNFα. Conclusion: Celecoxib can protect cartilage in OA by inhibiting NF-κB activation and IL-1β and TNF release, and decreasing cell apoptosis in inflammatory environment.

miR-155 Regulates GSK-3β Expression and Affects Cartilage Matrix Degradation in the Pathogenesis of Osteoarthritis

2019 ◽  
Vol 9 (8) ◽  
pp. 1133-1139
Author(s):  
Xianjun Chen ◽  
Lin Shi ◽  
Qingjiang Pang ◽  
Xiao Yu ◽  
Ji Yang
Keyword(s):  
Caspase 3 ◽  
Sham Group ◽  
Cartilage Matrix ◽  
Cartilage Tissue ◽  
Control Group ◽  
Traumatic Amputation ◽  
Normal Cartilage ◽  
Pathway Activity ◽  
Col2a1 Expression ◽  
Gsk 3Β

Abnormal expression of GSK-3β is associated with the pathogenesis of osteoarthritis (OA). The miR-155 expression in cartilage tissue of OA patients was significantly elevated. A relationship between miR-155 and GSK-3β is predicted by the software. This study investigated whether miR155 regulates GSK-3β expression, affects Wnt/β-catenin pathway activity in OA. The cartilage tissues of OA patients and normal cartilage tissues after traumatic amputation were collected. The OA rat model was established and divided into OA + antagomir control group, OA + miR-155 antagomir group followed by analysis of expression of miR-155, GSK-3β, β-catenin and COL2A1 by qRT-PCR, Hyp content by ELISA, caspase-3 activity, and GSK-3β, β-catenin, COL2A1 expression by western blot. Compared to control group, the expression of miR-155 and -catenin in cartilage tissue of OA patients was significantly elevated and GSK-3β level was reduced. There was a targeted regulation relationship between miR-155 and GSK-3β. OA group had significantly higher miR-155 and β-catenin expression and lower GSK-3 and COL2A1 level in the cartilage than sham group. Compared with OA + antagomir control group, miR-155 and β-catenin expression and caspase-3 activity in OA + miR-155 antagomir group were significantly decreased, with increased expression of GSK3β and COL2A1 and reduced Hyp content. Increased miR-155 expression can decrease GSK-3β expression, enhance Wnt/β-catenin pathway activity, promote the degradation and destruction of cartilage matrix and inhibit miR-155 expression, thus ameliorating the development and progress of OA.

Effect of miR-9 on Chondrocyte Apoptosis in Rats with Osteoarthritis by Regulating Notch1

2020 ◽  
Vol 10 (3) ◽  
pp. 371-378
Author(s):  
Xiao Zhong ◽  
Xiaodong Deng ◽  
Jian Luo ◽  
Ming Xiong ◽  
Wen Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Caspase 3 ◽  
Notch Signaling Pathway ◽  
Cartilage Matrix ◽  
Cartilage Tissue ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Matrix Degradation ◽  
Qrt Pcr ◽  
Protein Expressions

Objective: Notch1 is an important receptor in Notch signaling pathway. Abnormal Notch1 expression or function is associated with the pathogenesis of OA. There is evidence that the abnormal expression of miR-9 is related to the pathogenesis of OA. Bioinformatics analysis showed that there was a targeting relationship between miR-9 and Notch1’s 3′-UTR, suggesting that there might be a mutual regulation between them. In this study, we established an OA rat model to investigate whether miR-9 plays a role in regulating Notch1 expression, affecting cartilage matrix degradation and chondrocyte apoptosis in OA. Methods: OA model rats were divided into three groups: OA group, OA + agomir group, OA + miR-9 agomir group. The content of Hyp in articular fluid was measured by ELISA, the activity of caspase-3 was detected by kit, the mRNA expressions of miR-9, COL2A1, Notch1 and Hes5 was detected by qRT-PCR, and the protein expressions of Notch1 and Hes5 in articular cartilage was detected by Western blot. Chondrocytes were separated into control group, IL-1β +miR-NC group, IL-1β +miR-9 mimic group followed by analysis of mRNA expressions of miR-9, COL2A1, Notch1 and Hes5 were detected by qRT-PCR, protein expressions of Notch1 and Hes5 by Western blot, and cell apoptosis by flow cytometry. Results: Compared with Sham group, the levels of IL-1β , Hyp, Notch1, Hes5 and Caspase-3 in the synovial fluid of rats in OA group were increased significantly, while the mRNA expressions of miR-9, COL2A1 and Notch1 and Hes5 level in cartilage tissue were decreased significantly. Intra-articular injection of miR-9 agomir could significantly reduce the content of Hyp, the mRNA expressions of Notch1 and Hes5 and the activity of caspase-3 in cartilage tissue of OA rats, increase the mRNA expressions of miR-9 and COL2A1, and decrease the protein expressions of Notch1 and Hes5. After treated with IL-1β , the expressions of Notch1 and Hes5 were increased, the mRNA expressions of miR-9 and COL2A1 were decreased, and apoptosis of chondrocyte was increased in chondrocyte. After miR-9 mimic transfection, miR-9 and COL2A1 mRNA expressions were increased, Notch1 and Hes5 expressions were decreased, and apoptosis of chondrocyte was decreased under IL-1β treatment. Conclusion: Reduced miR-9 expression upregulates Notch1 expression and promotes the pathogenesis of OA. Increased miR-9 expression can inhibit Notch1 expression, reduce cartilage matrix degradation and inhibit chondrocyte apoptosis.

scholarly journals miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB

Cartilage ◽  
2021 ◽  
pp. 194760352110235
Author(s):  
Hongjun Zhang ◽  
Wendi Zheng ◽  
Du Li ◽  
Jia Zheng
Keyword(s):  
Caspase 3 ◽  
Cartilage Tissue ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Knee Cartilage ◽  
Before And After ◽  
Related Proteins ◽  
Human And Mouse

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

scholarly journals Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

2020 ◽  
Author(s):  
Guiqing Zhou ◽  
Jianhui Liu ◽  
Xiangyang Li ◽  
Yujian Sang ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Silica Nanoparticles ◽  
Caspase 3 ◽  
Reproductive Toxicity ◽  
Control Group ◽  
Caspase 9 ◽  
Protein Expressions ◽  
Underlying Mechanisms

Abstract Background: Silica nanoparticles (SiNPs) are found in environmental particulate matter and are proven to have adverse effects on fertility. The relationship and underlying mechanisms between miRNAs and apoptosis induced by SiNPs during spermatogenesis is currently ambiguous. Experimental design: The present study was designed to investigate the role of miRNA-450b-3p in the reproductive toxicity caused by SiNPs. In vivo, 40 male mice were randomly divided into control and SiNPs groups, 20 per group. The mice in the SiNPs group were administrated 20 mg/kg SiNPs by tracheal perfusion once every 5 days, for 35 days, and the control group were given the equivalent of a normal luminal saline. In vitro, spermatocyte cells were divided into 0 and 5 μg/mL SiNPs groups, after passaged for 30 generations, the GC-2spd cells in 5 μg/mL SiNPs groups were transfected with miRNA-450b-3p and its mimic and inhibitor. Results: In vivo, the results showed that SiNPs damaged tissue structures of testis, decreased the quantity and quality of the sperm, reduced the expression of miR-450b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, SiNPs obviously repressed the viability and increased the LDH level and apoptosis rate, decreased the levels of the miR-450b-3p, significantly enhanced the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3; while the mimic of miR-450b-3p reversed the changes induced by SiNPs, but inhibitor further promoted the effects induced by SiNPs.Conclusion: The result suggested that SiNPs could induce the spermatocyte apoptosis by inhibiting the miR-450b-3p expression to target promoting the MTCH2 resulting in activating mitochondrial apoptotic signaling pathways in the spermatocyte cells.

Resveratrol Reduces Cartilage Matrix Degradation and Affects Chondrocyte Apoptosis in Rats with Traumatic Arthritis

2020 ◽  
Vol 10 (2) ◽  
pp. 239-245
Author(s):  
Zhendong Liu ◽  
Kongbin Zhang ◽  
Yuesong Weng ◽  
Jianqiang Huang ◽  
Lu You
Keyword(s):  
Protein Expression ◽  
Protein Level ◽  
Cell Apoptosis ◽  
Cartilage Tissue ◽  
Chondrocyte Apoptosis ◽  
Therapeutic Effects ◽  
Matrix Degradation ◽  
Mankin Score ◽  
Joint Cavity ◽  
Traumatic Arthritis

Objective: Resveratrol (Resv) is a polyphenolic compound with anti-inflammatory, anti-oxidant, and other pharmacological effects in rheumatoid arthritis (RA). However, whether Resv has protective and therapeutic effects in post-traumatic arthritis (PTA) remains poorly understood. We explored the function of Resv in the treatment of PTA and reducing chondrocyte matrix degradation and chondrocyte apoptosis in PTA rats. Methods: The PTA rat model was established and divided into sham group and Resv gavage group. MMP-13 and Hyp contents in the joint cavity fluid were tested by ELISA. MMP-13 and COL2A1 protein expressions in the articular cartilage tissue were detected by Western blot. Mankin score was measured. The chondrocytes cultured in vitro and divided into control group, IL-1β group, and IL-1β + Resv group. Flow cytometry was adopted to detect cell apoptosis. Results: MMP-13 and Hyp contents were significantly increased, MMP-13 protein expression was significantly upregulated, COL2A1 protein expression was significantly reduced, while Mankin score was increased in PTA group in comparison to those in normal rats. Resv treatment significantly reduced MMP-13 protein expression and elevated COL2A1 protein level in cartilage tissue, decreased MMP-13 and Hyp contents in joint cavity fluid, and reduced Mankin score. After the treatment of IL-1β, the level of MMP-13 protein was significantly elevated, with decreased COL2A1 protein level in chondrocytes, and enhanced chondrocytes apoptosis. Resv intervention significantly inhibited MMP-13 protein and increased COL2A1 level in chondrocytes, and attenuated cell apoptosis. Conclusion: Resv inhibits MMP-13 expression, attenuates chondrocyte matrix degradation and apoptosis, indicating it plays a therapeutic value in treating PTA.

scholarly journals Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

2016 ◽  
Vol 40 (3-4) ◽  
pp. 621-632 ◽  
Author(s):  
Qing Zhao ◽  
Jianyong Yin ◽  
Zeyuan Lu ◽  
Yiwei Kong ◽  
Guangyuan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Vehicle Group ◽  
Control Group ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Contrast Induced Nephropathy ◽  
Sprague Dawley Rats ◽  
Hk2 Cells

Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.

scholarly journals Qufeng Xuanbi Formula ameliorates airway remodeling in asthmatic mice by suppressing airway smooth muscle cells proliferation through MEK/ERK signaling pathway

2021 ◽  
Author(s):  
Bohan Wang ◽  
Lingling Tang ◽  
Suofang Shi ◽  
Ying Yang ◽  
Xianhong Sun ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Lung Tissue ◽  
Airway Remodeling ◽  
Erk Signaling ◽  
Immunofluorescent Staining ◽  
Control Group ◽  
Airway Smooth Muscle Cells ◽  
Therapeutic Effects ◽  
Protein Expressions

Abstract BackgroundAsthma is a common chronic respiratory disease. Qufeng Xuanbi Formula (QFXBF), a Chinese herbal decoction, has shown efficiency for the management of asthma. The purpose of current study is to investigate the potential therapeutic effects of QFXBF for the treatment of asthma both in vitro and in vivo. MethodsPDGF-induced ASMCs proliferation model and MTT assay have been applied for exploring the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, OVA group, High QFXBF group, Low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). The mouse allergic asthma model has been established by intranasally administered ovalbumin (OVA) sensitization method. Morphological changes of the lung tissue have been examined by hematoxylin and eosin (H&E) staining and Masson’s staining. Finally, the protein expressions of α-SMA, PCNA, p-MEK1/2, MEK1/2, p-ERK1/2, and ERK1/2 in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. ResultsPDGF induced significant increase in viability of ASMCs. Compared with mice in control group, the airway walls and airway smooth muscle of mice in OVA group mice thickened, and the inflammatory cells around the bronchus increased significantly. Moreover, administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathologic changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment of QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA and PCNA. ConclusionQFXBF can inhibit the proliferation of ASMCs via suppressing the MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.

scholarly journals In Vivo Effects of Neostigmine and Physostigmine on Neutrophil Functions and Evaluation of Acetylcholinesterase and Butyrylcholinesterase as Inflammatory Markers during Experimental Sepsis in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Diane I. Bitzinger ◽  
Michael Gruber ◽  
Simon Tümmler ◽  
Manuela Malsy ◽  
Timo Seyfried ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Ache Activity ◽  
Sham Group ◽  
Saline Control ◽  
Control Group ◽  
Therapeutic Effects ◽  
Ros Production ◽  
Survival Times ◽  
Bche Activity ◽  
Pmn Functions

Introduction. Recent studies have shown that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may serve as important diagnostic and therapeutic targets in sepsis. Since polymorphonuclear neutrophils (PMNs) play a pivotal role in the early phase of sepsis, we evaluated the potential therapeutic effects of cholinesterase inhibitors on PMN functions during cecal ligation and puncture- (CLP-) induced sepsis and investigated the roles of AChE and BChE as inflammatory markers under standardized experimental conditions.Methods. Sham surgery or CLP was performed in male Wistar rats (n=60). Animals were randomized into four groups: physostigmine, 100 μg/kg; neostigmine, 75 μg/kg; 0.9% saline (control group); and sham group, each applied four times over 24 h. The levels of reactive oxygen species (ROS) production and CD11b/CD62l expression were quantified by flow cytometry att=0, 6, 15, 20, and 24 h. Blood gas analysis as well as AChE and BChE activity levels was measured by validated point-of-care measurements. Clinical scores and survival times were determined.Results. CLP induced a significant increase in ROS production and CD11b upregulation by rat PMNs. Treatment with physostigmine or neostigmine significantly reduced ROS production and CD11b upregulation by PMNs 20 h after CLP induction. In physostigmine-treated animals, survival times were significantly improved compared to the control animals, but not in neostigmine-treated animals. While AChE activity significantly decreased in the control animals att>6 h, AChE activity did not change in the sham group. BChE activity decreased att>20 hin the control animals.Conclusion. While AChE activity may serve as an acute inflammatory marker, BChE activity shows a delayed decrease. Administration of centrally acting physostigmine in CLP-induced sepsis in rats has protective effects on PMN functions and improves survival times, which may be of interest in clinical practice.

MiR-144-3p Regulates Lipopolysaccharide-Stimulated Chondrocyte Biological Behavior via Wingless-Related Integration Site/Beta-Catenin

2021 ◽  
Vol 11 (8) ◽  
pp. 1612-1617
Author(s):  
Nanxin Zhang ◽  
Kuangda Li ◽  
Qiong Han ◽  
Maohou Wu ◽  
Qiang Li
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Caspase 3 ◽  
Biological Behavior ◽  
Cartilage Tissue ◽  
Control Group ◽  
Beta Catenin ◽  
Activity Increase ◽  
Signaling Protein ◽  
Promote Cell Proliferation

Osteoarthritis (OA) gradually affects all joint tissues. Chondrocytes participate in osteoarthritis. However, the role and mechanism of MiR-144-3p on chondrocytes during the development of OA has not been elucidated. OA patients and normal bone and articular cartilage tissues were collected to measure MiR-144-3p level by Real-time PCR. Chondrocytes were divided into control group, LPS group (1 μg/ml lipopolysaccharide (LPS) was added to establish an osteoarthritis (OA) stimulation model, and MiR-144-3p inhibitor group which was transfected with MiR-144-3p inhibitor followed by analysis of cell proliferation by MTT, Caspase 3 activity, Wnt/β-catenin signaling protein expression by Western blot and TNF-α and IL-6 secretion by ELISA. MiR-144-3p was significantly upregulated in OA patients (P <0.05). In LPS group, MiR-144-3p was significantly upregulated, chondrocyte proliferation decreased, Caspase 3 activity increased, Wnt/β-catenin signaling protein decreased, and TNF-α and IL-6 secretion increased (P <0.05). MiR-144-3p inhibitor transfection can significantly down-regulate MiR-144-3p, promote cell proliferation, reduce Caspase 3 activity, increase Wnt/β-catenin signaling protein expression, and reduce TNF-α and IL-6 secretion (P <0.05). MiR-144-3p is upregulated in osteoarthritis cartilage tissue. Inhibition of MiR-144-3p can inhibit articular chondrocytes apoptosis under inflammatory condition, promote cell proliferation, and alleviate joint inflammation by regulating Wnt/β-catenin signaling pathway.

scholarly journals Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted Leukemia Model

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jae Gwang Park ◽  
Young-Jin Son ◽  
Tae Ho Lee ◽  
Nam Joon Baek ◽  
Deok Hyo Yoon ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Caspase 3 ◽  
In Vitro Cytotoxicity ◽  
Cordyceps Militaris ◽  
C6 Glioma Cells ◽  
Control Group ◽  
Therapeutic Effects ◽  
Anticancer Activities

Cordyceps militaris is used widely as a traditional medicine in East Asia. Although a few studies have attempted to elucidate the anticancer activities of C. militaris, the precise mechanism of C. militaris therapeutic effects is not fully understood. We examined the anticancer activities of C. militaris ethanolic extract (Cm-EE) and its cellular and molecular mechanisms. For this purpose, a xenograft mouse model bearing murine T cell lymphoma (RMA) cell-derived cancers was established to investigate in vivo anticancer mechanisms. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, immunoblotting analysis, and flow cytometric assay were employed to check in vitro cytotoxicity, molecular targets, and proapoptotic action of Cm-EE. Interestingly, cancer sizes and mass were reduced in a C. militaris-administered group. Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3β (p-GSK3β) and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3β-related caspase-3-dependent apoptosis.

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