Ursolic Acid in Cancer Treatment and Metastatic Chemoprevention: From Synthesized Derivatives to Nanoformulations in Preclinical Studies

2019 ◽  
Vol 19 (4) ◽  
pp. 245-256 ◽  
Author(s):  
Junjie Zou ◽  
Juanfang Lin ◽  
Chao Li ◽  
Ruirui Zhao ◽  
Lulu Fan ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Cancer Metastasis ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Cancer Drug ◽  
Therapeutic Effects ◽  
Candidate Drug ◽  
Wide Range ◽  
Anti Cancer ◽  
Tumor Growth And Metastasis

Background:Cancer metastasis has emerged as a major public health threat that causes majority of cancer fatalities. Traditional chemotherapeutics have been effective in the past but suffer from low therapeutic efficiency and harmful side-effects. Recently, it has been reported ursolic acid (UA), one of the naturally abundant pentacyclic triterpenes, possesses a wide range of biological activities including anti-inflammatory, anti-atherosclerotic, and anti-cancer properties. More importantly, UA has the features of low toxicity, liver protection and the potential of anti-cancer metastasis.Objective:This article aimed at reviewing the great potential of UA used as a candidate drug in the field of cancer therapy relating to suppression of tumor initiation, progression and metastasis.Methods:Selective searches were conducted in Pubmed, Google Scholar and Web of Science using the keywords and subheadings from database inception to December 2017. Systemic reviews are summarized here.Results:UA has exhibited chemopreventive and therapeutic effects of cancer mainly through inducing apoptosis, inhibiting cell proliferation, preventing tumor angiogenesis and metastatic. UA nanoformulations could enhance the solubility and bioavailability of UA as well as exhibit better inhibitory effect on tumor growth and metastasis.Conclusion:The information presented in this article can provide useful references for further studies on making UA a promising anti-cancer drug, especially as a prophylactic metastatic agent for clinical applications.

scholarly journals Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update

2020 ◽  
Vol 21 (16) ◽  
pp. 5920 ◽  
Author(s):  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe
Keyword(s):  
Ursolic Acid ◽  
Clinical Medicine ◽  
Biological Activities ◽  
Therapeutic Effects ◽  
Pharmacological Activities ◽  
Pentacyclic Triterpenoid ◽  
Anti Cancer ◽  
Pharmacologically Active ◽  
Derivatives Of ◽  
Cell Signaling Pathways

Ursolic acid is a pharmacologically active pentacyclic triterpenoid derived from medicinal plants, fruit, and vegetables. The pharmacological activities of ursolic acid have been extensively studied over the past few years and various reports have revealed that ursolic acid has multiple biological activities, which include anti-inflammatory, antioxidant, anti-cancer, etc. In terms of cancer treatment, ursolic acid interacts with a number of molecular targets that play an essential role in many cell signaling pathways. It suppresses transformation, inhibits proliferation, and induces apoptosis of tumor cells. Although ursolic acid has many benefits, its therapeutic applications in clinical medicine are limited by its poor bioavailability and absorption. To overcome such disadvantages, researchers around the globe have designed and developed synthetic ursolic acid derivatives with enhanced therapeutic effects by structurally modifying the parent skeleton of ursolic acid. These structurally modified compounds display enhanced therapeutic effects when compared to ursolic acid. This present review summarizes various synthesized derivatives of ursolic acid with anti-cancer activity which were reported from 2015 to date.

scholarly journals Tannic Acid-Lung Fluid Assemblies Promote Interaction and Delivery of Drugs to Lung Cancer Cells

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 111 ◽  
Author(s):  
Elham Hatami ◽  
Prashanth Nagesh ◽  
Pallabita Chowdhury ◽  
Subhash Chauhan ◽  
Meena Jaggi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tannic Acid ◽  
Biological Activities ◽  
The United States ◽  
Water Soluble ◽  
Cancer Drug ◽  
Major Barrier ◽  
Lung Fluid ◽  
Wide Range ◽  
Anti Cancer

Lung cancer (LC) is one of the leading causes of death in both men and women in the United States. Tannic acid (TA), a water-soluble polyphenol, exhibits a wide range of biological activities. TA has received much attention as a promising compound in the biomaterial and drug delivery fields. Lung fluid (LF) is a major barrier for distribution of drugs to the lungs. Therefore, the purpose of this study was to examine TA interaction with LF for effective delivery of anti-cancer drug molecules via pulmonary delivery. The extent of adsorption of LF proteins by TA was revealed by fluorescence quenching in fluorescence spectroscopy. The presence of LF in TA-LF complexes was noticed by the presence of protein peaks at 1653 cm−1. Both protein dot and SDS-PAGE analysis confirmed LF protein complexation at all TA concentrations employed. A stable particle TA-LF complex formation was observed through transmission electron microscopy (TEM) analysis. The complexation pattern measured by dynamic light scattering (DLS) indicated that it varies depending on the pH of the solutions. The degree of LF presence in TA-LF complexes signifies its interactive behavior in LC cell lines. Such superior interaction offered an enhanced anti-cancer activity of drugs encapsulated in TA-LF complex nanoformulations. Our results indicate that TA binds to LF and forms self-assemblies, which profoundly enhance interaction with LC cells. This study demonstrated that TA is a novel carrier for pharmaceutical drugs such as gemcitabine, carboplatin, and irinotecan.

scholarly journals Black Garlic and Its Bioactive Compounds on Human Health Diseases: A Review

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5028
Author(s):  
Tanvir Ahmed ◽  
Chin-Kun Wang
Keyword(s):  
Human Health ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
Water Soluble ◽  
Therapeutic Effects ◽  
Organosulfur Compounds ◽  
Wide Range ◽  
Anti Cancer ◽  
Future Challenges ◽  
Anti Inflammation

Black garlic (BG) is a form of aged garlic obtained from raw garlic (Allium sativum) via Millard reaction under high temperature (60–90 °C) and humidity (70–90%) for a period of time. Several studies reported higher contents of water-soluble antioxidants compounds (S-allyl cysteine, S-allyl-mercapto cysteine), 5-hydroxymethylfurfural, organosulfur compounds, polyphenol, volatile compounds, and products of other Millard reactions compared to fresh garlic after the thermal processing. Recent studies have demonstrated that BG and its bioactive compounds possess a wide range of biological activities and pharmacological properties that preserve and show better efficacy in preventing different types of diseases. Most of these benefits can be attributed to its anti-oxidation, anti-inflammation, anti-obesity, hepatoprotection, hypolipidemia, anti-cancer, anti-allergy, immunomodulation, nephroprotection, cardiovascular protection, and neuroprotection. Substantial studies have been conducted on BG and its components against different common human diseases in the last few decades. Still, a lot of research is ongoing to find out the therapeutic effects of BG. Thus, in this review, we summarized the pre-clinical and clinical studies of BG and its bioactive compounds on human health along with diverse bioactivity, a related mode of action, and also future challenges.

Structure-Bioactivity Relationship Study of Xanthene Derivatives: A Brief Review

2020 ◽  
Vol 16 (8) ◽  
pp. 1071-1077
Author(s):  
Aref G. Ghahsare ◽  
Zahra S. Nazifi ◽  
Seyed M.R. Nazifi
Keyword(s):  
Biological Activities ◽  
Cyclic Compound ◽  
Research Field ◽  
Pharmaceutical Chemistry ◽  
Therapeutic Effects ◽  
Main Research ◽  
Research Fields ◽  
Xanthene Derivatives ◽  
Anti Cancer ◽  
Heterocyclic Derivatives

: Over the last decades, several heterocyclic derivatives compounds have been synthesized or extracted from natural resources and have been tested for their pharmaceutical activities. Xanthene is one of these heterocyclic derivatives. These compounds consist of an oxygen-containing central heterocyclic structure with two more cyclic structures fused to the central cyclic compound. It has been shown that xanthane derivatives are bioactive compounds with diverse activities such as anti-bacterial, anti-fungal, anti-cancer, and anti-inflammatory as well as therapeutic effects on diabetes and Alzheimer. The anti-cancer activity of such compounds has been one of the main research fields in pharmaceutical chemistry. Due to this diverse biological activity, xanthene core derivatives are still an attractive research field for both academia and industry. This review addresses the current finding on the biological activities of xanthene derivatives and discussed in detail some aspects of their structure-activity relationship (SAR).

Natural Sesquiterpene Lactones in the Prevention and Treatment of Inflammatory Disorders and cancer: A Systematic Study of this Emerging Therapeutic Approach based on Chemical and Pharmacological Aspect

2020 ◽  
Vol 17 (9) ◽  
pp. 1102-1116
Author(s):  
Sudip Kumar Mandal ◽  
Utsab Debnath ◽  
Amresh Kumar ◽  
Sabu Thomas ◽  
Subhash Chandra Mandal ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Biological Activities ◽  
Sesquiterpene Lactones ◽  
Structural Diversity ◽  
Cancer Drug ◽  
Cancer Drug Discovery ◽  
Anti Cancer ◽  
Drug Discovery Program ◽  
Anti Inflammatory ◽  
Family Based

Background and Introduction: Sesquiterpene lactones are a class of secondary metabolite that contains sesquiterpenoids and lactone ring as pharmacophore moiety. A large group of bioactive secondary metabolites such as phytopharmaceuticals belong to this category. From the Asteraceae family-based medicinal plants, more than 5,000 sesquiterpene lactones have been reported so far. Sesquiterpene lactone-based pharmacophore moieties hold promise for broad-spectrum biological activities against cancer, inflammation, parasitic, bacterial, fungal, viral infection and other functional disorders. Moreover, these moiety based phytocompounds have been highlighted with a new dimension in the natural drug discovery program worldwide after the 2015 Medicine Nobel Prize achieved by the Artemisinin researchers. Objective: These bitter substances often contain an α, β-unsaturated-γ-lactone as a major structural backbone, which in recent studies has been explored to be associated with anti-tumor, cytotoxic, and anti-inflammatory action. Recently, the use of sesquiterpene lactones as phytomedicine has been increased. This study will review the prospect of sesquiterpene lactones against inflammation and cancer. Methods: Hence, we emphasized on the different features of this moiety by incorporating its structural diversity on biological activities to explore structure-activity relationships (SAR) against inflammation and cancer. Results: How the dual mode of action such as anti-inflammatory and anti-cancer has been exhibitedby these phytopharmaceuticals will be forecasted in this study. Furthermore, the correlation of anti-inflammatory and anti-cancer activity executed by the sesquiterpene lactones for fruitful phytotherapy will also be revealed in the present review in the milieu of pharmacophore activity relation and pharmacodynamics study as well. Conclusion: So, these metabolites are paramount in phytopharmacological aspects. The present discussion on the future prospect of this moiety based on the reported literature could be a guide for anti-inflammatory and anti-cancer drug discovery programs for the upcoming researchers.

Functional investigation of a highly conserved aspartate residue in the anti -cancer drug efflux transport protein MRP1

2018 ◽  
Author(s):  
Graeme Mullins
Keyword(s):  
Abc Transporters ◽  
Double Mutant ◽  
Transmembrane Helix ◽  
Salt Bridge ◽  
Multidrug Resistant ◽  
Site Directed Mutagenesis ◽  
Cancer Drug ◽  
Wide Range ◽  
Anti Cancer ◽  
Membrane Spanning

Multidrug Resistant Protein 1 (MRP1 or ABCC1) belongs to a subclass of ATP-binding cassette (ABC) transporters that export a wide range of metabolites and xenobiotics across the plasma membrane. Increased expression of MRP1 in cancer cells enhances efflux of many anti-cancer agents, giving rise to multidrug resistant tumours. The purpose of this study was to investigate the function of an aspartate (Asp) amino acid that is highly conserved in all MRP-related proteins by mutating it and determining the consequences of doing so. Asp430 lies at the interface of the cytoplasm and a transmembrane helix in the first membrane-spanning domain of MRP1. Previous studies have shown that when Asp430 is mutated, the protein becomes unstable and is degraded.Because this Asp430 is highly conserved in many MRP-related ABC transporters and because structural homology models of human MRP1 predict that Asp430 is in close proximity to Arg433, we hypothesized that a salt bridge between these two a mino acids could be essential for proper folding and stability of the protein during its biosynthesis. Using site -directed mutagenesis, these two amino acids were interchanged to probe the existence of such an interaction. Thus a double mutant where Asp430 was mutated to Arg, and Arg433 was mutated to Asp was created, and the resultant mutant protein (D430R/R433D) was tested for its ability to be detected in mammalian cells by gel electrophoresis and immunoblotting. Our results show differences between the migration patterns of double and single mutants that are compatible with differences in the glycosylation levels of MRP1. However the fact that D430R and the R433D mutants don’t share the same migration pattern, together with the variation in migration bet ween D430 wild type and Supported by CIHR MOP-10519the double mutant D430R/R433D indicate that the possibility of a salt bridge can be discarded.Supported by CIHR MOP-10519

scholarly journals Andrographolide, A Natural Antioxidant: An Update

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 571 ◽  
Author(s):  
Eugenie Mussard ◽  
Annabelle Cesaro ◽  
Eric Lespessailles ◽  
Brigitte Legrain ◽  
Sabine Berteina-Raboin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Herbal Remedy ◽  
Biological Activities ◽  
Lung Infection ◽  
Andrographis Paniculata ◽  
Natural Antioxidant ◽  
Nuclear Factor ◽  
Wide Range ◽  
Anti Cancer ◽  
Antioxidant Mechanisms

Traditionally, Andrographis paniculata has been used as an herbal remedy for lung infection treatments. Its leaves contain a diterpenoid labdane called andrographolide responsible for a wide range of biological activities such as antioxidant, anti-inflammatory, and anti-cancer properties. This manuscript is a brief review of the antioxidant mechanisms and the regulation of the Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling pathway by andrographolide.

scholarly journals Targeting microRNAs with thymoquinone: a new approach for cancer therapy

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Mina Homayoonfal ◽  
Zatollah Asemi ◽  
Bahman Yousefi
Keyword(s):  
Gene Expression ◽  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
World Health ◽  
Therapeutic Effects ◽  
Black Cumin ◽  
Small Noncoding Rnas ◽  
Wide Range ◽  
Anti Cancer ◽  
Cancer Agent

AbstractCancer is a global disease involving transformation of normal cells into tumor types via numerous mechanisms, with mortality among all generations, in spite of the breakthroughs in chemotherapy, radiotherapy and/or surgery for cancer treatment. Since one in six deaths is due to cancer, it is one of the overriding priorities of world health. Recently, bioactive natural compounds have been widely recognized due to their therapeutic effects for treatment of various chronic disorders, notably cancer. Thymoquinone (TQ), the most valuable constituent of black cumin seeds, has shown anti-cancer characteristics in a wide range of animal models. The revolutionary findings have revealed TQ’s ability to regulate microRNA (miRNA) expression, offering a promising approach for cancer therapy. MiRNAs are small noncoding RNAs that modulate gene expression by means of variation in features of mRNA. MiRNAs manage several biological processes including gene expression and cellular signaling pathways. Accordingly, miRNAs can be considered as hallmarks for cancer diagnosis, prognosis and therapy. The purpose of this study was to review the various molecular mechanisms by which TQ exerts its potential as an anti-cancer agent through modulating miRNAs.

scholarly journals β-Asarone Increases Chemosensitivity by Inhibiting Tumor Glycolysis in Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Heyun Tao ◽  
Xuelian Ding ◽  
Jian Wu ◽  
Shenlin Liu ◽  
Wei Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Biological Activities ◽  
Hypoxia Inducible Factor ◽  
Chinese Herb ◽  
Lactic Dehydrogenase ◽  
Inhibitory Effect ◽  
Pyruvate Dehydrogenase Kinase ◽  
Dependent Manner ◽  
Tumor Glycolysis ◽  
Wide Range

β-asarone is the main active ingredient of the Chinese herb Rhizoma Acori Tatarinowii, which exhibits a wide range of biological activities. It was confirmed to be an efficient cytotoxic agent against gastroenteric cancer cells. However, the exact mechanism of β-asarone in gastric cancer (GC) remains to be elucidated. The present study showed the inhibitory effect of β-asarone on three types of different differentiation stage GC cell lines (MGC803, SGC7901, and MKN74) in a dose-dependent manner. Meanwhile, the synergistic sensitivity of β-asarone and cisplatin was confirmed by using the median-effect principle. Flow cytometry assay revealed that under both normoxia and CoCl2-induced hypoxia conditions, β-asarone can induce apoptosis of GC cells, which can block GC cells in the cell cycle G2/M phase, showing obvious subdiploid peak. Moreover, the activity of lactic dehydrogenase (LDH), an enzyme that plays an important role in the final step of tumor glycolysis, was significantly decreased in GC cells following treatment with β-asarone. Mechanistically, β-asarone can reduce pyruvate dehydrogenase kinase (PDK) 1, phospho(p)-PDK1, PDK4, hypoxia-inducible factor 1-α (HIF1α), c-myc, STAT5, and p-STAT5 expression, which revealed how β-asarone affects tumor glycolysis. In conclusion, the present study provided evidence in support of the hypothesis that the increase of chemotherapy sensitization by β-asarone is associated with the inhibition of tumor glycolysis.

Fastidious Anatomization of Biota Procured Compounds on Cancer Drug Discovery

2020 ◽  
Vol 21 (5) ◽  
pp. 354-363
Author(s):  
Anand Thirupathi ◽  
Chandra M. Shanmugavadivelu ◽  
Sampathkumar Natarajan
Keyword(s):  
Natural Products ◽  
Side Effects ◽  
Cancer Therapy ◽  
Biological Activities ◽  
Drug Approval ◽  
Current Treatment ◽  
New Drugs ◽  
Cancer Drug ◽  
Synthetic Drugs ◽  
Wide Range

Background: Natural products are the rootstock for identifying new drugs since ancient times. In comparison with synthetic drugs, they have abounding beneficial effects in bestowing protection against many diseases, including cancer. Cancer has been observed as a major threat in recent decades, and its prevalence is expected to increase over the next decades. Also, current treatment methods in cancer therapy such as radiation therapy and chemotherapy cause severe adverse side effects among the cancer population. Therefore, it is exigent to find a remedy without any side effects. Methods: In recent years, research has focused on obtaining naturally derived products to encounter this complication. The current pace of investigations, such as gene identification and advancement in combinatorial chemistry, leads to the aberrant access to a wide range of new synthetic drugs. In fact, natural products act as templates in structure predictions and synthesis of new compounds with enhanced biological activities. Results: Recent developments in genomics have established the importance of polymorphism, which implies that patients require different drugs for their treatment. This demands the discovery of a large number of drugs, but limited sources restrict the pharmaceutical industry to overcome these major obstacles. The use of natural products and their semisynthetic and synthetic analogues could alleviate these problems. However, the lack of standardization in terms of developing methods for evaluating the chemical composition, efficacy, isolation and international approval is still a major limitation in this field. In the past few years, several drug-approval authorities, including the FDA and WHO have allowed using these naturally derived compounds in humans. Conclusion: In this review, we described the use of some natural products from plant and marine sources in cancer treatment and shed some light on semi-synthetic and synthetic compounds derived from natural sources used in cancer therapy.

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