A water-soluble parthenolide analogue suppresses in vivo prostate cancer growth by targeting NFκB and generating reactive oxygen species

The Prostate ◽  
2010 ◽  
Vol 70 (10) ◽  
pp. 1074-1086 ◽  
Author(s):  
Rajasubramaniam Shanmugam ◽  
Praveen Kusumanchi ◽  
Liang Cheng ◽  
Peter Crooks ◽  
Sundar Neelakantan ◽  
...  
2010 ◽  
Vol 128 (10) ◽  
pp. 2481-2494 ◽  
Author(s):  
Rajasubramaniam Shanmugam ◽  
Praveen Kusumanchi ◽  
Hitesh Appaiah ◽  
Liang Cheng ◽  
Peter Crooks ◽  
...  

Nanomedicine ◽  
2019 ◽  
Vol 14 (19) ◽  
pp. 2567-2578 ◽  
Author(s):  
Hyeryeon Oh ◽  
Jin Sil Lee ◽  
Daekyung Sung ◽  
Jin Hyung Lee ◽  
Sang Hyun Moh ◽  
...  

Aim: Prussian blue nanoparticles (PB NPs) have been reported as excellent antioxidant agents owing to their ability to scavenge reactive oxygen species. However, their poor stability in vivo limits their use in biomedical applications. Materials & methods: In this study, we developed chitosan-templated PB NPs using water-soluble chitosan samples with molecular weights ranging from 3 to 100 kDa, which stabilized the PB NPs and improved their antioxidant activity. Results & conclusion: The chitosan-templated PB NPs coordinated with the optimal chitosan molecular weight had uniform sphere-like particles, improved stability and effective scavenging activity of in vitro reactive oxygen species generation in murine fibroblast cells stimulated by oxidative stress agents without any cytotoxicity, implying that they could be promising antioxidant agents.


2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.


2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhuochao Liu ◽  
Hongyi Wang ◽  
Chuanzhen Hu ◽  
Chuanlong Wu ◽  
Jun Wang ◽  
...  

AbstractIn this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.


2008 ◽  
Vol 84 (11) ◽  
pp. 945-955 ◽  
Author(s):  
Eui Kwan Koh ◽  
Byung-Kyu Ryu ◽  
Dong-Young Jeong ◽  
Iel-Soo Bang ◽  
Myung Hee Nam ◽  
...  

2019 ◽  
Vol 20 (18) ◽  
pp. 4556 ◽  
Author(s):  
Hanna Zielinska-Blizniewska ◽  
Przemyslaw Sitarek ◽  
Anna Merecz-Sadowska ◽  
Katarzyna Malinowska ◽  
Karolina Zajdel ◽  
...  

Obesity is a complex disease of great public health significance worldwide: It entails several complications including diabetes mellitus type 2, cardiovascular dysfunction and hypertension, and its prevalence is increasing around the world. The pathogenesis of obesity is closely related to reactive oxygen species. The role of reactive oxygen species as regulatory factors in mitochondrial activity in obese subjects, molecules taking part in inflammation processes linked to excessive size and number of adipocytes, and as agents governing the energy balance in hypothalamus neurons has been examined. Phytotherapy is the traditional form of treating health problems using plant-derived medications. Some plant extracts are known to act as anti-obesity agents and have been screened in in vitro models based on the inhibition of lipid accumulation in 3T3-L1 cells and activity of pancreatic lipase methods and in in vivo high-fat diet-induced obesity rat/mouse models and human models. Plant products may be a good natural alternative for weight management and a source of numerous biologically-active chemicals, including antioxidant polyphenols that can counteract the oxidative stress associated with obesity. This review presents polyphenols as natural complementary therapy, and a good nutritional strategy, for treating obesity without serious side effects.


2021 ◽  
Vol 22 (14) ◽  
pp. 7509
Author(s):  
Hai Huang ◽  
Jun-Koo Yi ◽  
Su-Geun Lim ◽  
Sijun Park ◽  
Haibo Zhang ◽  
...  

Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor.


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