Peptides as Potential Anticancer Agents

2019 ◽  
Vol 19 (17) ◽  
pp. 1491-1511 ◽  
Author(s):  
Shams Aaghaz ◽  
Vivek Gohel ◽  
Ahmed Kamal
Keyword(s):  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
The Body ◽  
Production Costs ◽  
Cell Subpopulation ◽  
Anticancer Compounds ◽  
Normal Tissues ◽  
Oncogenic Mutations ◽  
Multiple Cell

Cancer consists of heterogeneous multiple cell subpopulation which at a later stage develop resistant phenotypes, which include resistance to pro-apoptotic stimuli and/or cytotoxic resistance to anticancer compounds. The property of cancerous cells to affect almost any part of the body categorizes cancer to many anatomic and molecular subtypes, each requiring a particular therapeutic intervention. As several modalities are hindered in a variety of cancers and as the cancer cells accrue varied types of oncogenic mutations during their progression the most likely benefit will be obtained by a combination of therapeutic agents that might address the diverse hallmarks of cancer. Natural compounds are the backbone of cancer therapeutics owing to their property of affecting the DNA impairment and restoration mechanisms and also the gene expression modulated via several epigenetic molecular mechanisms. Bioactive peptides isolated from flora and fauna have transformed the arena of antitumour therapy and prompt progress in preclinical studies is promising. The difficulties in creating ACP rest in improving its delivery to the tumour site and it also must maintain a low toxicity profile. The substantial production costs, low selectivity and proteolytic stability of some ACP are some of the factors hindering the progress of peptide drug development. Recently, several publications have tried to edify the field with the idea of using peptides as adjuvants with established drugs for antineoplastic use. This review focuses on peptides from natural sources that precisely target tumour cells and subsequently serve as anticancer agents that are less toxic to normal tissues.

scholarly journals Molecular mechanisms of control of differentiation of regulatory t-lymphocytes by exogenous melatonin

2019 ◽  
Vol 484 (2) ◽  
pp. 224-227
Author(s):  
N. S. Glebezdina ◽  
A. A. Olina ◽  
I. V. Nekrasova ◽  
E. M. Kuklina
Keyword(s):  
T Cells ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
The Body ◽  
Membrane Receptors ◽  
Cell Subpopulation ◽  
Exogenous Melatonin ◽  
Regulatory T Lymphocytes ◽  
Treg Differentiation

We investigated the role of epiphyseal hormone melatonin in the differentiation of naive CD4+T cells into regulatory T cells (Treg). The hormone at physiological and pharmacological concentrations inhibited Treg differentiation, decreasing both the proportion of CD4+FOXP3+ cells in the culture and the level of TGF‑β, the key cytokine for this T cell subpopulation. The inhibitory effect of exogenous melatonin was due to its interaction with the membrane receptors MT1 and MT2. At the same time, the signals realized through RORa — the nuclear receptor for melatonin — stimulated Treg formation; however, they were considerably weaker than the signals from the membrane receptors and were overlapped by the latter. Since the Treg subpopulation plays an important role in physiological and pathological processes in the body, the revealed effects of melatonin should be taken into account in its therapeutic use.

scholarly journals Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3219 ◽  
Author(s):  
Ahmed El-Sharkawy ◽  
Ahmed Malki
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Active Form ◽  
The Body ◽  
Skeletal Health ◽  
Therapeutic Benefits ◽  
Vitamin D Signaling

Vitamin D and its active metabolites are important nutrients for human skeletal health. UV irradiation of skin converts 7-dehydrocholesterol into vitamin D3, which metabolized in the liver and kidneys into its active form, 1α,25-dihydroxyvitamin D3. Apart from its classical role in calcium and phosphate regulation, scientists have shown that the vitamin D receptor is expressed in almost all tissues of the body, hence it has numerous biological effects. These includes fetal and adult homeostatic functions in development and differentiation of metabolic, epidermal, endocrine, neurological and immunological systems of the body. Moreover, the expression of vitamin D receptor in the majority of immune cells and the ability of these cells to actively metabolize 25(OH)D3 into its active form 1,25(OH)2D3 reinforces the important role of vitamin D signaling in maintaining a healthy immune system. In addition, several studies have showed that vitamin D has important regulatory roles of mechanisms controlling proliferation, differentiation and growth. The administration of vitamin D analogues or the active metabolite of vitamin D activates apoptotic pathways, has antiproliferative effects and inhibits angiogenesis. This review aims to provide an up-to-date overview on the effects of vitamin D and its receptor (VDR) in regulating inflammation, different cell death modalities and cancer. It also aims to investigate the possible therapeutic benefits of vitamin D and its analogues as anticancer agents.

scholarly journals The RND1 Small GTPase: Main Functions and Emerging Role in Oncogenesis

2019 ◽  
Vol 20 (15) ◽  
pp. 3612
Author(s):  
Laetitia Mouly ◽  
Julia Gilhodes ◽  
Anthony Lemarié ◽  
Elizabeth Cohen-Jonathan Moyal ◽  
Christine Toulas ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Rho Gtpase ◽  
Current Knowledge ◽  
Cancer Therapeutics ◽  
Predictive Marker ◽  
Bound State ◽  
Small Gtpase ◽  
Mrna Levels

The Rho GTPase family can be classified into classic and atypical members. Classic members cycle between an inactive Guanosine DiPhosphate -bound state and an active Guanosine TriPhosphate-bound state. Atypical Rho GTPases, such as RND1, are predominantly in an active GTP-bound conformation. The role of classic members in oncogenesis has been the subject of numerous studies, while that of atypical members has been less explored. Besides the roles of RND1 in healthy tissues, recent data suggest that RND1 is involved in oncogenesis and response to cancer therapeutics. Here, we present the current knowledge on RND1 expression, subcellular localization, and functions in healthy tissues. Then, we review data showing that RND1 expression is dysregulated in tumors, the molecular mechanisms involved in this deregulation, and the role of RND1 in oncogenesis. For several aggressive tumors, RND1 presents the features of a tumor suppressor gene. In these tumors, low expression of RND1 is associated with a bad prognosis for the patients. Finally, we highlight that RND1 expression is induced by anticancer agents and modulates their response. Of note, RND1 mRNA levels in tumors could be used as a predictive marker of both patient prognosis and response to anticancer agents.

scholarly journals Chemotherapy and Dietary Phytochemical Agents

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Katrin Sak
Keyword(s):  
Side Effects ◽  
Cancer Therapy ◽  
Anticancer Agents ◽  
Multiple Organ ◽  
The Body ◽  
Cytotoxic Agents ◽  
Adverse Side Effects ◽  
Chemotherapy Drugs ◽  
Normal Tissues ◽  
Organ Systems

Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way.

NOB1: A Potential Biomarker or Target in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 1081-1089
Author(s):  
Weiwei Ke ◽  
Zaiming Lu ◽  
Xiangxuan Zhao
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Binding Protein ◽  
Tumor Development ◽  
Anticancer Therapy ◽  
Research Progress ◽  
Normal Tissues ◽  
Potential Biomarker

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

Anticancer Agents Based on Vulnerable Components in a Signalling Pathway

2020 ◽  
Vol 20 (10) ◽  
pp. 886-907 ◽  
Author(s):  
Ankur Vaidya ◽  
Shweta Jain ◽  
Sanjeev Sahu ◽  
Pankaj Kumar Jain ◽  
Kamla Pathak ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Dna Methyltransferase ◽  
Leucine Zipper ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
Sphingosine Kinase 2 ◽  
Family Protein ◽  
Rational Combination ◽  
Protein Kinase Akt ◽  
Parp 1

Traditional cancer treatment includes surgery, chemotherapy, radiotherapy and immunotherapy that are clinically beneficial, but are associated with drawbacks such as drug resistance and side effects. In quest for better treatment, many new molecular targets have been introduced in the last few decades. Finding new molecular mechanisms encourages researchers to discover new anticancer agents. Exploring the mechanism of action also facilitates anticipation of potential resistance mechanisms and optimization of rational combination therapies. The write up describes the leading molecular mechanisms for cancer therapy, including mTOR, tyrosine Wee1 kinase (WEE1), Janus kinases, PI3K/mTOR signaling pathway, serine/threonine protein kinase AKT, checkpoint kinase 1 (Chk1), maternal embryonic leucine-zipper kinase (MELK), DNA methyltransferase I (DNMT1), poly (ADP-ribose) polymerase (PARP)-1/-2, sphingosine kinase-2 (SK2), pan-FGFR, inhibitor of apoptosis (IAP), murine double minute 2 (MDM2), Bcl-2 family protein and reactive oxygen species 1 (ROS1). Additionally, the manuscript reviews the anticancer drugs currently under clinical trials.

Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

2019 ◽  
Vol 19 (10) ◽  
pp. 765-781
Author(s):  
Seema Rohilla ◽  
Harish Dureja ◽  
Vinay Chawla
Keyword(s):  
Adverse Effects ◽  
Anticancer Agents ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Vital Role ◽  
Normal Cells ◽  
Normal Tissues ◽  
Organ Specific ◽  
Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

Engineering “Antimicrobial Peptides” and Other Peptides to Modulate Protein-Protein Interactions in Cancer

2020 ◽  
Vol 20 (32) ◽  
pp. 2970-2983
Author(s):  
Samuel J.S. Rubin ◽  
Nir Qvit
Keyword(s):  
Antimicrobial Peptides ◽  
Protein Interactions ◽  
Anticancer Agents ◽  
Cancer Therapeutics ◽  
Target Cells ◽  
Protein Protein Interactions ◽  
Peptide Backbone ◽  
Modified Peptides ◽  
Selective Death ◽  
Drug Leads

Antimicrobial peptides (AMPs) are a class of peptides found across a wide array of organisms that play key roles in host defense. AMPs induce selective death in target cells and orchestrate specific or nonspecific immune responses. Many AMPs exhibit native anticancer activity in addition to antibacterial activity, and others have been engineered as antineoplastic agents. We discuss the use of AMPs in the detection and treatment of cancer as well as mechanisms of AMP-induced cell death. We present key examples of cathelicidins and transferrins, which are major AMP families. Further, we discuss the critical roles of protein-protein interactions (PPIs) in cancer and how AMPs are well-suited to target PPIs based on their unique drug-like properties not exhibited by small molecules or antibodies. While peptides, including AMPs, can have limited stability and bioavailability, these issues can be overcome by peptide backbone modification or cyclization (e.g., stapling) and by the use of delivery systems such as cellpenetrating peptides (CPPs), respectively. We discuss approaches for optimizing drug properties of peptide and peptidomimetic leads (modified peptides), providing examples of promising techniques that may be applied to AMPs. These molecules represent an exciting resource as anticancer agents with unique therapeutic advantages that can target challenging mechanisms involving PPIs. Indeed, AMPs are suitable drug leads for further development of cancer therapeutics, and many studies to this end are underway.

Role of Phytochemicals in the Treatment of Breast Cancer: Natural Swords battling Cancer Cells

2021 ◽  
Vol 16 ◽  
Author(s):  
Rajni Sawanny ◽  
Sheersha Pramanik ◽  
Unnati Agarwal
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Low Cost ◽  
Epigallocatechin Gallate ◽  
Cancer Therapeutics ◽  
Treatment Modalities ◽  
Breast Cancer Patients ◽  
Scientific Validity ◽  
Phytochemical Study ◽  
Treat Breast Cancer

: Breast cancer is the most common type of malignancy among ladies (around 30% of newly diagnosed patients every year). To date, various modern treatment modalities for breast cancer, such as radiotherapy, surgical method, hormonal therapy, and chemotherapeutic drug utilisation, are available. However, adverse drug reactions, therapeutic resistance, metastasis, or cancer reoccurrence chances remain the primary causes of mortality for breast cancer patients. To overcome all the potential drawbacks, we need to investigate novel techniques and strategies previously not considered and treat breast cancer effectively with safety and efficacy. For centuries, we utilise phytochemicals to treat various diseases because of their safety, low-cost & least or no side effects. Recently, naturally produced phytochemicals gain immense attention as potential breast cancer therapeutics because of their ideal characteristics; for instance, they operate via modulating molecular pathways associated with cancer growth and progression. The primary mechanism involves inhibition of cell proliferation, angiogenesis, migration, invasion, increasing anti-oxidant status, initiation of the arrest of the cell cycle, and apoptosis. Remedial viability gets effectively enhanced when phytochemicals work as adjuvants with chemotherapeutic drugs. This comprehensive review revolves around the latest chemopreventive, chemotherapeutic, and chemoprotective treatments with their molecular mechanisms to treat breast cancer by utilising phytochemicals such as vinca alkaloids, resveratrol, curcumin, paclitaxel, silibinin, quercetin, genistein and epigallocatechin gallate. The authors wish to extend the field of phytochemical study for its scientific validity and its druggability.

Cytotoxic Activity and DNA Binding Property of New Aminopyrimidine Derivatives

2020 ◽  
Vol 17 (5) ◽  
pp. 640-654
Author(s):  
Hamidreza Akrami ◽  
Bibi Fatemeh Mirjalili ◽  
Omidreza Firuzi ◽  
Azadeh Hekmat ◽  
Ali Akbar Saboury ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Lymphoblastic Leukemia ◽  
Cd Spectroscopy ◽  
Myelogenous Leukemia ◽  
Breast Adenocarcinoma ◽  
Binding Property ◽  
Anticancer Compounds ◽  
Calf Thymus ◽  
Dna Binding Property

Background: Chromene and anilinopyrimidine heterocyclics are attractive anticancer compounds that have inspired many researchers to design novel derivatives bearing improved anticancer activity. Methods: A series of pyrimidine-fused benzo[f]chromene derivatives 6a-x were synthesized as anticancer hybrids of 1H-benzo[f]chromenes and anilinopyrimidines. The inhibitory activity of the synthesized compounds 6a-x against cell viability of human chronic myelogenous leukemia (K562), human acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma (MCF-7) cell lines was evaluated using MTT assay. The interaction of the most promising compound with calf-thymus DNA was also studied using spectrometric titrations and Circular Dichroism (CD) spectroscopy. Results: Most compounds showed promising activity against tested cell lines. Among them, 2,4- dimethoxyanilino derivative 6g exhibited the best profile of activity against tested cell lines (IC50s = 1.6-6.1 μM) with no toxicity against NIH3T3 normal cell (IC50 >200 μM). The spectrometric studies exhibited that compound 6g binds to DNA strongly and may change DNA conformation significantly, presumably via a groove binding mechanism. Conclusion: The results of this study suggest that the prototype compound 6g can be considered as a novel lead compound for the design and discovery of novel anticancer agents.

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