Copper complexes as antitumor agents: in vitro and in vivo evidences

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucia M. Balsa ◽  
Enrique J. Baran ◽  
Ignacio E. León
Keyword(s):  
Copper Complexes ◽  
Antitumor Agents ◽  
Essential Element ◽  
Design Synthesis ◽  
Copper Compounds ◽  
Comprehensive Knowledge ◽  
The Relationship

: Copper is an essential element for most aerobic organisms, with an important function as a structural and catalytic cofactor, and in consequence, it is implicated in several biological actions. The relevant aspects of chemistry and biochemistry and the importance of copper compounds in medicine give us a comprehensive knowledge of the multifaceted applications of copper in physiology and physiopathology. In this review, we present an outline of the chemistry and the antitumor properties of copper complexes on breast, colon, and lung cancer cells focus on the role of copper in cancer, the relationship between structure-activity, molecular targets, and the study of the mechanism of action involved in its anticancer activity. This overview is expected to contribute to understanding the design, synthesis, uses of copper complexes as antitumor agents in the most common cancers.

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

scholarly journals Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24376-24385 ◽  
Author(s):  
Wen-Bin Kuang ◽  
Ri-Zhen Huang ◽  
Yi-Lin Fang ◽  
Gui-Bin Liang ◽  
Chen-Hui Yang ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Agents ◽  
Quinoline Derivatives ◽  
Apoptotic Response ◽  
Design Synthesis ◽  
Cycle Arrest ◽  
In Vivo Antitumor Activity ◽  
Combination Principle

A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives were designed and synthesized as antitumor agents under the combination principle. The antitumor activity and mechanisms were then evaluated.

scholarly journals E3 Ubiquitin Ligase TRIM29 Promotes Pancreatic Cancer Growth and Progression via Stabilizing Yes-associated Protein 1

2021 ◽  
Author(s):  
Xueqiang Deng ◽  
Xiaowei Fu ◽  
Hong Teng ◽  
Lu Fang ◽  
Bo Liang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Cycle Progression ◽  
Nude Mouse Model ◽  
Cycle Progression ◽  
Signal Cascade ◽  
The Relationship ◽  
Precise Role

Abstract Background: Pancreatic cancer (PC) is one of the most fatal digestive system cancers. tripartite motif-29 (TRIM29) has been reported as oncogene in several human cancers. However, the precise role and underlying signal cascade of TRIM29 in PC progression remain unclear.Methods: Western blot, qRT-PCR and immunohistochemistry were used to analyze TRIM29 and Yes-associated protein 1 (YAP1) levels. CCK8 assays, EdU assays and flow cytometry were designed to explore the function and potential mechanism of TRIM29 and YAP1 in the proliferation of PC. Next, a nude mouse model of PC was established for validating the roles of TRIM29 and YAP1 in vivo. The relationship among TRIM29 and YAP1 was explored by co-immunoprecipitation and in vitro ubiquitination assay.Results: TRIM29 and YAP1 was significantly upregulated in PC patient samples, and TRIM29 expression was closely related to a malignant phenotype and poorer overall survival (OS) of PC patients. Functional assays revealed that TRIM29 knockdown suppresses cell growth, arrests cell cycle progression and promotes cell apoptosis of PC cells in vivo and in vitro. Furthermore, the rescue experiments demonstrated that TRIM29-induced proliferation is dependent on YAP1 in PC cells. Mechanistically, TRIM29 regulates YAP1 expression by directly binding to YAP1, and reduced its ubiquitination and degradation.Conclusion: Taken together, these results identify a novel mechanism used by PC growth, and provide insight regarding the role of TRIM29 in PC.

scholarly journals TREM2, Driving the Microglial Polarization, Has a TLR4 Sensitivity Profile After Subarachnoid Hemorrhage

2021 ◽  
Vol 9 ◽  
Author(s):  
Yangchun Hu ◽  
Chao Li ◽  
Xiaojian Wang ◽  
Weiwei Chen ◽  
Yu Qian ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Neuroprotective Effect ◽  
Neurological Dysfunction ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Microglial Polarization ◽  
The Relationship

Increasing evidence suggests that triggering receptor expressed on myeloid cells 2 (TREM2) is implicated in the pathophysiology of neuroinflammation. The aim here was to investigate the neuroprotective role of TREM2 and its regulatory mechanism after subarachnoid hemorrhage (SAH). TREM2 siRNA was administered to measure the detrimental role of TREM2 in mediating microglial polarization in vivo and in vitro after experimental SAH. The relationship between Toll-like receptor 4 (TLR4) signaling and TREM2 was further explored. The soluble TREM2 from the cerebrospinal fluid (CSF) of patients with SAH was detected. The results showed that TREM2 mainly located in the microglia and presented a markedly delayed elevation after SAH. TREM2 knockdown triggered increased pro-inflammatory productions, aggravated microglial activities, and further exacerbated neurological dysfunction after SAH. Significantly, TLR4 knockout increased the expression of TREM2, accompanied by ameliorated neuroinflammation and improved neurological function. Corresponding to different clinical Hunt–Hess grades, obviously enhanced accumulation of soluble TREM2 was detected in the CSF of patients with SAH. TREM2 played a pivotal role in mediating microglial polarization after SAH, and the neuroprotective effect of TREM2 might be potentially suppressed by the hyperactive TLR4 in the early phase of SAH. Pharmacological targeting of TREM2 may be a promising strategy for SAH therapy.

scholarly journals Remodeling of hepatic stellate cells orchestrated the stroma-derived oxaliplatin-resistance through CCN3 paracrine in hepatocellular carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xia Liao ◽  
Yang Bu ◽  
Fan Chang ◽  
Fengan Jia ◽  
Ge Song ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Stellate Cells ◽  
Critical Role ◽  
Stellate Cells ◽  
Clinical Samples ◽  
Pathway Activation ◽  
The Relationship

Abstract Background Hepatic stellate cells (HSCs) have a key role in fibrogenesis and in the filtrates of the hepatocellular carcinoma (HCC) stroma, in which they are remodeled and play a critical role in HCC progression. However, the precise role of HSCs trending, infiltration and paracrine in orchestrating the stroma-derived oxaliplatin-resistance in HCC is still vague. Methods The chemo-resistant models were established to explore the correlation between HSC cells and the condition of chemoresistance. The HCC clinical samples were collected to confirm this phenomenon. Then, the relationship between secretory CCN3 from oxaliplatin-resistant HCC and the infiltration of HSCs in associated HCC microenvironment was evaluated. Finally, the role and mechanism of HSCs remodeling in the orchestration of oxaliplatin-resistant HCC were explored. Results The increased infiltration of HSCs and collagen accumulation were found in the microenvironment of oxaliplatin-resistant HCC. The cDNA profiles of the oxaliplatin-resistant HCC was reanalyzed, and CCN3 was one of the significantly increased genes. In HCC clinical samples, the levels of CCN3 and α-SMA are positively correlated, and high expression of CCN3 and α-SMA are positively associated with malignant phenotype and poor prognosis. Then the enhanced abilities of migration and proliferation of HSCs, and elevation of the cytokines paracrine from HSCs relating to HCC malignancy were proved in vitro and in vivo, and which were related to CCN3-ERK signaling pathway activation. Conclusions HSCs remodeling are positively related to CCN3 paracrine in hepatocellular carcinoma, which orchestrated the stroma-derived resistance to chemotherapy in HCC.

scholarly journals EGFR-AS1 Promotes Bladder Cancer Progression by Upregulating EGFR

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Anbang Wang ◽  
Aimin Jiang ◽  
Xinxin Gan ◽  
Zheng Wang ◽  
Jinming Huang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Diagnostic Marker ◽  
Bladder Cancer Cells ◽  
The Relationship ◽  
Proliferation And Invasion

Long noncoding RNAs play an essential role in bladder cancer progression. The role of long noncoding RNA EGFR-AS1 in bladder cancer needs further study. We used clinical specimens to analyze the relationship between EGFR-AS1 and bladder cancer patients’ characteristics. The functional experiments and mechanism studies were performed using qRT-PCR, transwell assay, survival analysis, and correlation analysis. We found that high expression of EGFR-AS1 was nearly related to aggressive bladder cancer and indicated poor prognosis for patients. The functional experiments in vivo and in vitro suggested that EGFR-AS1 promoted the proliferation and invasion of bladder cancer cells. Mechanically, EGFR-AS1 promoted the expression of EGFR by inhibiting the degradation of EGFR mRNA, thereby promoting the metastasis of bladder cancer. In addition, EGFR-AS1/EGFR may be involved in the immune-related pathways of bladder cancer. These studies indicate that the EGFR-AS1/EGFR pathway may be a potential diagnostic marker and therapeutic target for bladder cancer.

scholarly journals LncRNA RBM5-AS1 Promotes Osteosarcoma Cell Proliferation, Migration, and Invasion

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Biyong Deng ◽  
Runsang Pan ◽  
Xin Ou ◽  
Taizhe Wang ◽  
Weiguo Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Western Blotting ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Pediatric Age Group ◽  
The Relationship

Purpose. Osteosarcoma (Os) is the most frequent malignant tumor of the bone in the pediatric age group, and accumulating evidences show that lncRNAs play a key role in the development of Os. Thus, we investigated the role of RBM5-AS1 and its molecular mechanism. Methods. The expression of RBM5-AS1 in Os tissues and cell lines was detected by real-time polymerase chain reaction (QPCR). The effect of RBM5-AS1 on the proliferation of Os cells was detected using CCK8 assays and flow cytometry. The effect of RBM5-AS1 on the migration and invasion of Os cells was detected by transwell assays. And we performed QPCR and western blotting assays to investigate the relationship between RBM5-AS1 and RBM5. Finally, western blotting assays were performed to explore the mechanism of RBM5. Results. LncRNA RBM5-AS1 was overexpressed in the Os tissues and cell lines. And lncRNA RBM5-AS1 promoted Os cell proliferation, migration, and invasion in vitro and tumor growth in vivo. LncRNA RBM5-AS1 targets RBM5 in Os cells. Conclusion. To sum up, the results showed that lncRNA RBM5-AS1 promotes cell proliferation, migration, and invasion in Os.

Tubulin Inhibitors Binding to Colchicine-Site: A Review from 2015 to 2019

2020 ◽  
Vol 27 (40) ◽  
pp. 6787-6814 ◽  
Author(s):  
Lin-Ying Xia ◽  
Ya-Liang Zhang ◽  
Rong Yang ◽  
Zhong-Chang Wang ◽  
Ya-Dong Lu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Agents ◽  
Structural Features ◽  
Design Synthesis ◽  
Antiproliferative Effects ◽  
Tubulin Inhibitors ◽  
Relationship Of ◽  
Podophyllotoxin Derivatives

Due to the three domains of the colchicine-site which is conducive to the combination with small molecule compounds, colchicine-site on the tubulin has become a common target for antitumor drug development, and accordingly, a large number of tubulin inhibitors binding to the colchicine-site have been reported and evaluated over the past years. In this study, tubulin inhibitors targeting the colchicine-site and their application as antitumor agents were reviewed based on the literature from 2015 to 2019. Tubulin inhibitors were classified into ten categories according to the structural features, including colchicine derivatives, CA-4 analogs, chalcone analogs, coumarin analogs, indole hybrids, quinoline and quinazoline analogs, lignan and podophyllotoxin derivatives, phenothiazine analogs, N-heterocycle hybrids and others. Most of them displayed potent antitumor activity, including antiproliferative effects against Multi-Drug-Resistant (MDR) cell lines and antivascular properties, both in vitro and in vivo. In this review, the design, synthesis and the analysis of the structure-activity relationship of tubulin inhibitors targeting the colchicine-site were described in detail. In addition, multi-target inhibitors, anti-MDR compounds, and inhibitors bearing antitumor activity in vivo are further listed in tables to present a clear picture of potent tubulin inhibitors, which could be beneficial for medicinal chemistry researchers.

scholarly journals Microbiota and Immune-Mediated Skin Diseases—An Overview

2019 ◽  
Vol 7 (9) ◽  
pp. 279 ◽  
Author(s):  
Adrian Catinean ◽  
Maria Adriana Neag ◽  
Andrei Otto Mitre ◽  
Corina Ioana Bocsan ◽  
Anca Dana Buzoianu
Keyword(s):  
Autoimmune Diseases ◽  
Beneficial Effect ◽  
Skin Diseases ◽  
Experimental Studies ◽  
Immune Mediated ◽  
The Impact ◽  
The Relationship

In recent years, increased attention has been paid to the relationship between microbiota and various diseases, especially immune-mediated diseases. Because conventional therapy for many autoimmune diseases is limited both in efficacy and safety, there is an increased interest in identifying nutraceuticals, particularly probiotics, able to modulate the microbiota and ameliorate these diseases. In this review, we analyzed the research focused on the role of gut microbiota and skin in immunity, their role in immune-mediated skin diseases (IMSDs), and the beneficial effect of probiotics in patients with this pathology. We selected articles published between 2009 and 2019 in PubMed and ScienceDirect that provided information regarding microbiota, IMSDs and the role of probiotics in these diseases. We included results from different types of studies including observational and interventional clinical trials or in vivo and in vitro experimental studies. Our results showed that probiotics have a beneficial effect in changing the microbiota of patients with IMSDs; they also influence disease progression. Further studies are needed to better understand the impact of new therapies on intestinal microbiota. It is also important to determine whether the microbiota of patients with autoimmune diseases can be manipulated in order to restore homeostasis of the microbiota.

Sign in / Sign up

Export Citation Format

Share Document