scholarly journals Potential anticancer activity of curcumin analogs containing sulfone on human cancer cells

2016 ◽  
Vol 68 (1) ◽  
pp. 125-133 ◽  
Author(s):  
Qiuyan Zhang ◽  
Dongli Li ◽  
Yue Liu ◽  
Hui Wang ◽  
Changyuan Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Human Cancer ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Curcumin Analogs ◽  
Phosphorylated Akt ◽  
Transcription 3

Three curcumin analogs(S1-S3) containing sulfone were investigated for their effects on human prostate cancer PC-3, colon cancer HT-29, lung cancer H1299 and pancreatic cancer BxPC-3 cells. The three compounds were approximately 16-to 96-fold more active than curcumin in these cell lines as determined by the MTT assay. The effects of these compounds on cell growth were further studied in prostate cancer PC-3 cells in both two dimensional (2D) and three dimensional (3D) cultures. S1-S3strongly inhibited the growth and induced cell death in PC-3 cells, and the effects of these compounds were associated with suppression of nuclear factor kappa B (NF-?B) transcriptional activity. Moreover, treatment of PC-3 cells with all three compounds caused a decrease in the level of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) (Tyr705),but not p-STAT3(Ser727). Only S1and S2decreased the presence of phosphorylated Akt (p-Akt) in PC-3 cells. These curcumin analogs warrant further in vivo studies for anticancer activities in suitable animal models.

Magnesium Chloride is an Effective Therapeutic Agent for Prostate Cancer

2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain
Keyword(s):  
Prostate Cancer ◽  
Magnesium Chloride ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Condensation ◽  
Myosin Ii ◽  
In Vivo Studies ◽  
Migration Speed ◽  
Mesenchymal Transition

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.

Nanocurcumin: A Double-Edged Sword for Microcancers

2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam
Keyword(s):  
Intracellular Signaling ◽  
Dosage Forms ◽  
The Body ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Anticancer Activities ◽  
Road Map ◽  
Anticancer Effects

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

scholarly journals A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

2021 ◽  
Vol 22 (16) ◽  
pp. 8372
Author(s):  
Ana María Zárate ◽  
Christian Espinosa-Bustos ◽  
Simón Guerrero ◽  
Angélica Fierro ◽  
Felipe Oyarzún-Ampuero ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Antitumour Activity ◽  
Anticancer Compounds ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis Inducer ◽  
Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

scholarly journals Three-Dimensional Zirconia-Based Scaffolds for Load-Bearing Bone-Regeneration Applications: Prospects and Challenges

Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3207
Author(s):  
Kumaresan Sakthiabirami ◽  
Vaiyapuri Soundharrajan ◽  
Jin-Ho Kang ◽  
Yunzhi Peter Yang ◽  
Sang-Won Park
Keyword(s):  
Bone Regeneration ◽  
Biological Activities ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
High Mechanical Strength ◽  
Real World Applications ◽  
3D Fabrication ◽  
Dental Applications

The design of zirconia-based scaffolds using conventional techniques for bone-regeneration applications has been studied extensively. Similar to dental applications, the use of three-dimensional (3D) zirconia-based ceramics for bone tissue engineering (BTE) has recently attracted considerable attention because of their high mechanical strength and biocompatibility. However, techniques to fabricate zirconia-based scaffolds for bone regeneration are in a stage of infancy. Hence, the biological activities of zirconia-based ceramics for bone-regeneration applications have not been fully investigated, in contrast to the well-established calcium phosphate-based ceramics for bone-regeneration applications. This paper outlines recent research developments and challenges concerning numerous three-dimensional (3D) zirconia-based scaffolds and reviews the associated fundamental fabrication techniques, key 3D fabrication developments and practical encounters to identify the optimal 3D fabrication technique for obtaining 3D zirconia-based scaffolds suitable for real-world applications. This review mainly summarized the articles that focused on in vitro and in vivo studies along with the fundamental mechanical characterizations on the 3D zirconia-based scaffolds.

scholarly journals Cancer interception by interceptor molecules: mechanistic, preclinical and human translational studies with chlorophylls

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Roderick H. Dashwood
Keyword(s):  
Immune Modulation ◽  
Human Cancer ◽  
Alkylating Agents ◽  
Radical Scavenging ◽  
Molecular Complexes ◽  
Antimutagenic Activity ◽  
Human Cancer Cells ◽  
Translational Studies ◽  
Salmonella Assay

AbstractBefore ‘cancer interception’ was first advocated, ‘interceptor molecules’ had been conceived as a sub-category of preventive agents that interfered with the earliest initiation steps in carcinogenesis. Three decades ago, a seminal review cataloged over fifty synthetic agents and natural products that were known or putative interceptor molecules. Chlorophylls and their derivatives garnered much interest based on the potent antimutagenic activity in the Salmonella assay, and the subsequent mechanistic work that provided proof-of-concept for direct molecular complexes with planar aromatic carcinogens. As the ‘interceptor molecule’ hypothesis evolved, mechanistic experiments and preclinical studies supported the view that chlorophylls can interact with environmental heterocyclic amines, aflatoxins, and polycyclic aromatic hydrocarbons to limit their uptake and bioavailability in vivo. Support also came from human translational studies involving ultralow dose detection in healthy volunteers, as well as intervention in at-risk subjects. Antimutagenic and antigenotoxic effects of natural and synthetic chlorophylls against small alkylating agents also highlighted the fact that non-interceptor mechanisms existed. This gave impetus to investigations broadly related to free radical scavenging, anti-inflammatory effects, immune modulation and photodynamic therapy. Therapeutic aspects of chlorophylls also were investigated, with evidence for cell cycle arrest and apoptosis in human cancer cells. As the science has evolved, new mechanistic leads continue to support the use and development of chlorophylls and their porphyrin derivatives for cancer interception, beyond the initial interest as interceptor molecules.

scholarly journals The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3088
Author(s):  
Mariana Matias ◽  
Jacinta O. Pinho ◽  
Maria João Penetra ◽  
Gonçalo Campos ◽  
Catarina Pinto Reis ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Drug Evaluation ◽  
Three Dimensional ◽  
Experimental Models ◽  
In Vivo Studies ◽  
Murine Models ◽  
In Vivo Experiments ◽  
Novel Therapeutic Strategies

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.

scholarly journals Cardiac Glycoside Ouabain Exerts Anticancer Activity via Downregulation of STAT3

2021 ◽  
Vol 11 ◽  
Author(s):  
Jie Du ◽  
Lijun Jiang ◽  
Fuqiang Chen ◽  
Huantao Hu ◽  
Meijuan Zhou
Keyword(s):  
Cardiac Glycosides ◽  
Human Cancer ◽  
Cancer Therapeutics ◽  
Initiation Factor ◽  
Ros Generation ◽  
Dna Double Strand Breaks ◽  
Atpase Inhibitor ◽  
Anticancer Activities ◽  
Downstream Target ◽  
Human Cancer Cells

Cardiac glycosides are plant-derived steroid-like compounds which have been used for the treatment of cardiovascular diseases. Ouabain, a cardiotonic steroid and specific Na+/K+-ATPase inhibitor, has been rediscovered for its potential use in the treatment of cancer. However, the cellular targets and anticancer mechanism of ouabain in various cancers remain largely unexplored. In this study, we confirmed the cytotoxic effects of ouabain on several cancer cell lines. Further examination revealed the increase of apoptosis, intracellular ROS generation and DNA double-strand breaks induced by ouabain treatment. Besides, ouabain effectively suppressed STAT3 expression as well as phosphorylation in addition to block STAT3-mediated transcription and downstream target proteins. Interestingly, these inhibitory activities seemed to be independent of the Na+/K+-ATPase. Furthermore, we found that ouabain inhibited protein synthesis through regulation of the eukaryotic initiation factor 4E (eIF4E) and eIF4E binding protein 1 (4EBP1). Taken together, our study provided a novel molecular insight of anticancer activities of ouabain in human cancer cells, which could raise the hope of using cardiac glycosides for cancer therapeutics more rational.

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