A Purified Extract from Clematis mandshurica Prevents Adenoviral-TRAIL Induced Apoptosis on Rat Articular Chondrocytes

2008 ◽  
Vol 36 (02) ◽  
pp. 399-410 ◽  
Author(s):  
Sung Won Lee ◽  
Hye Jeong Lee ◽  
Jeong Bon Moon ◽  
Sun Mee Choi ◽  
Duk Kyu Kim ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Articular Chondrocytes ◽  
Down Regulation ◽  
Phosphorylated Akt ◽  
Oa Chondrocytes ◽  
Novel Strategy ◽  
Induced Apoptosis

Since TNF-related apoptosis inducing ligand (TRAIL) is one of several apoptotic stimuli on articular chondrocytes, the modulation of the mechanism mediated by TRAIL could be considered as a novel strategy for the treatment of osteoarthritis (OA). Previous studies demonstrated that Clematis mandshurica prevents staurosporin-induced apoptosis in articular chondrocytes. This study was undertaken to examine whether Clematis mandshurica could prevent TRAIL-induced apoptosis in articular chondrocytes. Our data show that Clematis mandshurica prevents adenoviral TRAIL (Ad-TRAIL)-induced apoptosis in primary cultured articular chondrocytes. Clematis mandshurica prevents Ad-TRAIL-induced down-regulation of 14-3-3 and phosphorylated Akt. In addition, Clematis mandshurica treatment prevents the Ad-TRAIL-induced reduction of the interactions between 14-3-3 with phospho-ser112-Bad and phospho-ser136-Bad, and BcL-xL with phospho-ser155-Bad. A better understanding of the mechanism underlying inhibition of apoptosis in OA chondrocytes by Clematis mandshurica might lead to the development of a new therapeutic strategy for OA.

Lobetyolin inhibits the proliferation of breast cancer cells via ASCT2 down-regulation-induced apoptosis

2021 ◽  
pp. 096032712110214
Author(s):  
Yansong Chen ◽  
Ye Tian ◽  
Gongsheng Jin ◽  
Zhen Cui ◽  
Wei Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glutamine Metabolism ◽  
Down Regulation ◽  
Anti Cancer ◽  
Induced Apoptosis ◽  
Glutamine Uptake

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 ( SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 ( SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3β signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

Down-regulation of p21Waf-1 protein facilitates IR- and UV-induced apoptosis in human squamous carcinoma cells

2004 ◽  
Author(s):  
Shinsuke Izumaru ◽  
Nobuyuki Arima ◽  
Yasuo Toyozumi ◽  
Seiya Kato ◽  
Minoru Morimatsu ◽  
...  
Keyword(s):  
Squamous Carcinoma ◽  
Carcinoma Cells ◽  
Down Regulation ◽  
Squamous Carcinoma Cells ◽  
Induced Apoptosis

scholarly journals Isorhynchophylline Protects PC12 Cells Against Beta-Amyloid-Induced Apoptosis via PI3K/Akt Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yan-Fang Xian ◽  
Zhi-Xiu Lin ◽  
Qing-Qiu Mao ◽  
Jian-Nan Chen ◽  
Zi-Ren Su ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Neuroprotective Effect ◽  
Protective Action ◽  
Protective Effects ◽  
Phosphorylated Akt ◽  
Induced Apoptosis

The neurotoxicity of amyloid-β(Aβ) has been implicated as a critical cause of Alzheimer’s disease. Isorhynchophylline (IRN), an oxindole alkaloid isolated fromUncaria rhynchophylla,exerts neuroprotective effect againstAβ25–35-induced neurotoxicityin vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of IRN againstAβ25–35-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Pretreatment with IRN significantly increased the cell viability, inhibited the release of lactate dehydrogenase and the extent of DNA fragmentation inAβ25–35-treated cells. IRN treatment was able to enhance the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3β(p-GSK-3β). Lithium chloride blockedAβ25–35-induced cellular apoptosis in a similar manner as IRN, suggesting that GSK-3βinhibition was involved in neuroprotective action of IRN. Pretreatment with LY294002 completely abolished the protective effects of IRN. Furthermore, IRN reversedAβ25–35-induced attenuation in the level of phosphorylated cyclic AMP response element binding protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor. These experimental findings unambiguously suggested that the protective effect of IRN againstAβ25–35-induced apoptosis in PC12 cells was associated with the enhancement of p-CREB expression via PI3K/Akt/GSK-3βsignaling pathway.

scholarly journals Aldo-Keto Reductase 1C3 Mediates Chemotherapy Resistance in Esophageal Adenocarcinoma via ROS Detoxification

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2403
Author(s):  
Chenghui Zhou ◽  
Zhefang Wang ◽  
Jiahui Li ◽  
Xiaolin Wu ◽  
Ningbo Fan ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Mrna Level ◽  
Chemotherapy Resistance ◽  
Poor Overall Survival ◽  
Akt Phosphorylation ◽  
Tumor Tissues ◽  
Novel Strategy ◽  
Induced Apoptosis ◽  
First Time ◽  
Eac Cells

Esophageal adenocarcinoma (EAC) is one of the most lethal malignancies, and limits promising treatments. AKR1C3 represents a therapeutic target to combat the resistance in many cancers. However, the molecular mechanism of AKR1C3 in the chemotherapy resistance of EAC is still unclear. We found that the mRNA level of AKR1C3 was higher in EAC tumor tissues, and that high AKR1C3 expression might be associated with poor overall survival of EAC patients. AKR1C3 overexpression decreased cell death induced by chemotherapeutics, while knockdown of AKR1C3 attenuated the effect. Furthermore, we found AKR1C3 was inversely correlated with ROS production. Antioxidant NAC rescued chemotherapy-induced apoptosis in AKR1C3 knockdown cells, while the GSH biosynthesis inhibitor BSO reversed a protective effect of AKR1C3 against chemotherapy. AKT phosphorylation was regulated by AKR1C3 and might be responsible for eliminating over-produced ROS in EAC cells. Intracellular GSH levels were modulated by AKR1C3 and the inhibition of AKT could reduce GSH level in EAC cells. Here, we reported for the first time that AKR1C3 renders chemotherapy resistance through controlling ROS levels via AKT signaling in EAC cells. Targeting AKR1C3 may represent a novel strategy to sensitize EAC cells to conventional chemotherapy.

scholarly journals Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NFkB/MDR1 pathway

2020 ◽  
Author(s):  
Yoshifumi Mizobuchi ◽  
Kenji Shono ◽  
Izumi Yamaguchi ◽  
Kohei Nakajima ◽  
Yuri Fujiwara ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Surgical Intervention ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Multidrug Resistant ◽  
Down Regulation ◽  
Sonodynamic Therapy ◽  
Glioma Model ◽  
A Site ◽  
Mouse Glioma

Abstract Glioblastoma (GBM) has high mortality rates because of extremely therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) is an emerging and promising approach combined with low-intensity ultrasonication (US) and PpIX as a sonosensitizer for cancer, whereas its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, a MDR1 inhibitor and augmented anti-tumor effects of SDT. MDR1 down-regulation via Akt/NF-kB pathway by celecoxib was confirmed, using a NF-kB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via Akt/NF-kB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.

scholarly journals Snail Switches 5-FU-induced Apoptosis to Necrosis through Akt/PKB Activation and p53 Down-regulation

2012 ◽  
Vol 22 (8) ◽  
pp. 1018-1023 ◽  
Author(s):  
Su-Yeon Lee ◽  
Hyun-Min Jeon ◽  
Min-Kyung Ju ◽  
Cho-Hee Kim ◽  
Eui-Kyong Jeong ◽  
...  
Keyword(s):  
Down Regulation ◽  
Induced Apoptosis
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