Role of cathepsin B in cancer progression: a potential target for coordination compounds

2021 ◽  
Vol 21 ◽  
Author(s):  
Amos Olalekan Akinyemi ◽  
George Bueno Santana Pereira ◽  
Fillipe Vieira Rocha
Keyword(s):  
Cancer Progression ◽  
Cysteine Protease ◽  
Cathepsin B ◽  
Coordination Compounds ◽  
Metal Compounds ◽  
Over Expression ◽  
Protease Enzyme ◽  
Different Types ◽  
Metallic Compounds

: A member of cathepsin enzymes called Cathepsin B, is a cysteine-protease enzyme that plays significant roles in metalloproteinase regulation. Cathepsin B stands out amidst other members of cathepsin because of its role in both normal body physiology and pathophysiology. Being an anti-apoptotic and a pro-apoptotic agent, Cathepsin B has been reported to have deleterious effects, especially when its expression, activities, and distribution are outrageous. The over-expression of cathepsin B is traceable to dysregulation of one or more regulated steps involved in its synthesis. Consequently, the over-expression of cathepsin B contributes to the pathogenesis of different types of cancers – a global menace. Interestingly, the synthesis of this enzyme has been reported to be inhibited by several metal compounds, thus, curbing its involvement in carcinogenesis. In this review, the synthesis, structure, localization, and roles of cathepsin B in carcinogenesis were explored. Likewise, we also discussed the capacity of metallic compounds to inhibit this enzyme. Metals such as gold, ruthenium, palladium, Iridium, and Tellurium demonstrated remarkable activity toward cathepsin B of different modes. A relationship between cytotoxicity and inhibition constants was observed.

scholarly journals The role of m6A modification in the biological functions and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiulin Jiang ◽  
Baiyang Liu ◽  
Zhi Nie ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Rna Modification ◽  
Biological Functions ◽  
Rna Methylation ◽  
Downstream Target ◽  
Different Types ◽  
M6a Rna Methylation

AbstractN6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

How Antimalarials and Antineoplastic Drugs can Interact in Combination Therapies: a Perspective on the Role of PPT1 Enzyme

2021 ◽  
Vol 22 ◽  
Author(s):  
Diana Duarte ◽  
Nuno Vale
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Antineoplastic Agents ◽  
Antimalarial Drugs ◽  
Antineoplastic Drugs ◽  
Anticancer Effects ◽  
Different Types ◽  
Important Pathway ◽  
Palmitoyl Protein Thioesterase

: Antimalarial drugs from different classes have demonstrated anticancer effects in different types of cancer cells, but their complete mode of action in cancer remains unknown. Recently, several studies reported the important role of palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme, as the molecular target of chloroquine and its derivates in cancer. It was also found that PPT1 is overexpressed in different types of cancer, such as breast, colon, etc. Our group has found a synergistic interaction between antimalarial drugs, such as mefloquine, artesunate and chloroquine and antineoplastic drugs in breast cancer cells, but the mechanism of action was not determined. Here, we describe the importance of autophagy and lysosomal inhibitors in tumorigenesis and hypothesize that other antimalarial agents besides chloroquine could also interact with PPT1 and inhibit the mechanistic target of rapamycin (mTOR) signalling, an important pathway in cancer progression. We believe that PPT1 inhibition results in changes in the lysosomal metabolism that result in less accumulation of antineoplastic drugs in lysosomes, which increases the bioavailability of the antineoplastic agents. Taken together, these mechanisms help to explain the synergism of antimalarial and antineoplastic agents in cancer cells.

scholarly journals N-cadherin antagonists as oncology therapeutics

2015 ◽  
Vol 370 (1661) ◽  
pp. 20140039 ◽  
Author(s):  
Orest W. Blaschuk
Keyword(s):  
Cell Adhesion ◽  
Cancer Progression ◽  
Structural Integrity ◽  
Cancer Therapies ◽  
Transmembrane Glycoprotein ◽  
Anti Cancer ◽  
Different Types ◽  
Poorly Differentiated ◽  
Novel Strategy

The cell adhesion molecule (CAM), N-cadherin, has emerged as an important oncology therapeutic target. N-cadherin is a transmembrane glycoprotein mediating the formation and structural integrity of blood vessels. Its expression has also been documented in numerous types of poorly differentiated tumours. This CAM is involved in regulating the proliferation, survival, invasiveness and metastasis of cancer cells. Disruption of N-cadherin homophilic intercellular interactions using peptide or small molecule antagonists is a promising novel strategy for anti-cancer therapies. This review discusses: the discovery of N-cadherin, the mechanism by which N-cadherin promotes cell adhesion, the role of N-cadherin in blood vessel formation and maintenance, participation of N-cadherin in cancer progression, the different types of N-cadherin antagonists and the use of N-cadherin antagonists as anti-cancer drugs.

Targeting Tumor-derived exosomes expressing CD73: new opportunities in the pathogenesis and treatment of cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Vajihe Taghdiri Nooshabadi ◽  
Samaneh Arab
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Development ◽  
Therapeutic Resistance ◽  
Intracellular Communication ◽  
Different Types ◽  
Therapeutic Protocols ◽  
Tumor Exosomes ◽  
Selection Of

: Tumor-derived exosomes contain biological contents such as proteins, lipids, RNA (miRNAs, mRNAs, lncRNA), and DNA for intracellular communication. Meanwhile, studies have shown the role of exosomes in cancer progression, metastasis, and therapeutic resistance. Furthermore, tumor exosomes have received growing attention due to their potential as novel therapeutic protocols for the treatment of cancers. Adenosine nucleoside, which is a derivative of ATP, is highly elevated in the tumor microenvironment by CD39 and CD73 enzymatic activity. Recently, it is distinguished that cancer cellderived exosomes carry CD39 and CD73 on their surface and may contribute to rising adenosine levels in the tumor microenvironment. In this review, we summarize the evidence of CD39/CD73-bearing exosomes and their role in cancer development, progression, invasion, angiogenesis, metastasis and their application in the selection of the appropriate strategy to treat different types of cancer.

Role of High Mobility Group Box1 in Pathogenesis of Hepatitis C Virus induced Hepatocellular Carcinoma

2020 ◽  
Vol EJMM29 (4) ◽  
pp. 135-141
Author(s):  
Nouran E. Samra ◽  
Shahira El-Etreby ◽  
Rasha H. El-Mahdy ◽  
Samah S. El-Kazzaz ◽  
Nariman M. El-Nashar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Nuclear Dna ◽  
Inflammatory Responses ◽  
High Mobility ◽  
Dna Binding Protein ◽  
High Mobility Group ◽  
Over Expression ◽  
Different Types

Hepatocellular carcinoma "HCC" is a leading cause of cancer mortality worldwide. High-mobility group box 1 "HMGB1" is a nuclear DNA-binding protein which involved in DNA stability, programmed cell death, immune response and inflammatory responses in HCV and HCC. Its over expression was revealed in HCC and different types of human cancers.

scholarly journals Fluctuating Roles of Matrix Metalloproteinase-9 in Oral Squamous Cell Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Suvi-Tuuli Vilen ◽  
Tuula Salo ◽  
Timo Sorsa ◽  
Pia Nyberg
Keyword(s):  
Cancer Progression ◽  
Protective Role ◽  
Cell Behavior ◽  
Metastasis Formation ◽  
Oral Cancers ◽  
Disease Prognosis ◽  
Different Types ◽  
Metalloproteinase 9 ◽  
Proliferation And Invasion

One hallmark of cancer is the degradation of the extracellular matrix (ECM), which is caused by proteinases. In oral cancers, matrix metalloproteinases (MMPs), especially MMP-9, are associated with this degradation. MMPs break down the ECM allowing cancer to spread; they also release various factors from their cryptic sites, including cytokines. These factors modulate cell behavior and enhance cancer progression by regulating angiogenesis, migration, proliferation, and invasion. The development of early metastases is typical for oral cancer, and increased MMP-9 expression is associated with a poor disease prognosis. However, many studies fail to relate MMP-9 expression with metastasis formation. Contrary to earlier models, recent studies show that MMP-9 plays a protective role in oral cancers. Therefore, the role of MMP-9 is complicated and may fluctuate throughout the different types and stages of oral cancers.

scholarly journals Selected Micro RNAs Regulate Drug Resistance Genes in Breast Cancer.

2021 ◽  
Author(s):  
Shumaila Zaib ◽  
Azra Yasmin ◽  
Nosheen Masood
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Progression Free Survival ◽  
Pten Gene ◽  
Over Expression ◽  
Micro Rnas ◽  
Exact Etiology

Abstract Background: Breast cancer initiation is an unresolved phenomenon although many genes are known to be involved in its initiation but its exact etiology is still unexplained in many aspects and recently microRNAs are found to regulate many genes expressions. Method: This case control study has been designed to evaluate the role of selected miRNAs in gene expression and subsequent association with drug resistance. Genetic polymorphisms were confirmed by PCR-SSCP followed by sequencing and microRNA expression was measured by realtime PCR with specific primers. Follow up was done for patients whose samples were used in the study. Results: This study revealed 15 germline mutations in mdr1, 5 in ABCG2, 8 in BRCA1 and 8 in PTEN gene. These mutations were significantly associated with breast cancer compared with control tissues (P<0.05). miR-21, miR-146a and miR-328 were over expressed whereas miR-451 was under expressed. Progression free survival (PFS) was linked with reduced polymorphisms in genes as well as microRNAs. Conclusion: Over expression of miRNA-21 and miRNA-146a may lead towards lower expression of PTEN and BRCA1 genes causing cancer progression. miRNA-328 and miRNA-451 reduced expression resulted in overexpressed ABCG2 and MDR1 genes in this study.

The Role of STAT3 Signaling in Different Types of Cancers: A Comprehensive Review

2020 ◽  
Vol 16 (3) ◽  
pp. 189-198
Author(s):  
Kaviarasan Lakshmanan ◽  
Gowramma Byran ◽  
Sravanthi Bandlamudi ◽  
Praveen Thaggikuppe Krishnamurthy
Keyword(s):  
Cancer Progression ◽  
Myeloid Leukemia ◽  
Inflammatory Responses ◽  
Vital Role ◽  
Signal Transducer ◽  
Stat3 Signaling ◽  
Solid Malignancies ◽  
Different Types ◽  
Tumor Growth And Metastasis

Signal transducer and activator of transcription (STAT3) is an important transcription factor capable of mediating or even driving cancer progression through hyperactivation or gain-offunction mutations. It plays a key role in regulating host immune and inflammatory responses and in the pathogenesis of many cancers. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a vital role in tumor growth and metastasis. Hyperactive STAT3 is also implicated in various hematopoietic and solid malignancies, such as chronic and acute myeloid leukemia, melanoma or prostate cancer. The classical understanding of STAT functions is linked to their phosphorylated parallel dimer conformation, in which they induce gene transcription. In this review, we discuss the functions and the roles of STAT3 signal in various types of cancers.

Causation, Causal Selection, and Causal Parity

2018 ◽  
Author(s):  
Anya Plutynski
Keyword(s):  
Cancer Progression ◽  
Research Program ◽  
Cellular Growth ◽  
Causal Relevance ◽  
Different Types ◽  
Causal Selection ◽  
Context Specific ◽  
Regulatory Controls ◽  
Causal Specificity

It is typical to refer to cancer as a “genetic” or “genomic” disease. This claim is ambiguous; one of the central goals of this chapter is to disambiguate this claim. I first distinguish different types of causal claims: claims about causal relevance, causal role, and causal specificity. As a backdrop to this discussion, I introduce what I call the “mechanistic research program” in cancer, according to which progression to cancer involves breakdowns in regulatory controls on gene expression in ways that affect cell birth and death. While this research program has been successful, it has downplayed the role of context in cancer progression, and the fact that disorderly cellular growth is affected by many pathways. I conclude by considering several philosophers’ accounts of “causal selection” and argue that ultimately the causal selection problem is not one but several different problems, requiring different, context-specific solutions.

scholarly journals The Microbiome and Its Implications in Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 206
Author(s):  
Hani Choudhry
Keyword(s):  
Cell Cycle ◽  
Cancer Immunotherapy ◽  
Cancer Progression ◽  
Physiological Responses ◽  
Cell Cycle Checkpoints ◽  
Diagnostic Tools ◽  
Different Types ◽  
Underlying Mechanisms ◽  
Therapy Strategies

Cancer is responsible for ~18 million deaths globally each year, representing a major cause of death. Several types of therapy strategies such as radiotherapy, chemotherapy and more recently immunotherapy, have been implemented in treating various types of cancer. Microbes have recently been found to be both directly and indirectly involved in cancer progression and regulation, and studies have provided novel and clear insights into the microbiome-mediated emergence of cancers. Scientists around the globe are striving hard to identify and characterize these microbes and the underlying mechanisms by which they promote or suppress various kinds of cancer. Microbes may influence immunotherapy by blocking various cell cycle checkpoints and the production of certain metabolites. Hence, there is an urgent need to better understand the role of these microbes in the promotion and suppression of cancer. The identification of microbes may help in the development of future diagnostic tools to cure cancers possibly associated with the microbiome. This review mainly focuses on various microbes and their association with different types of cancer, responses to immunotherapeutic modulation, physiological responses, and prebiotic and postbiotic effects.

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