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

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.

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

Current Cancer Drug Targets ◽

10.2174/1568009618666181016145940 ◽

2019 ◽

Vol 19 (4) ◽

pp. 245-256 ◽

Cited By ~ 6

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.

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

Molecules ◽

10.3390/molecules26165028 ◽

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.

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Testing the Addition of an Anti-cancer Drug, M6620, to the Usual Treatments (Carboplatin and Gemcitabine) and to Avelumab for Non-small Cell Lung Cancer

Case Medical Research ◽

10.31525/ct1-nct04216316 ◽

2020 ◽

Author(s):

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Cancer Drug ◽

Small Cell Lung ◽

Anti Cancer

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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

Letters in Drug Design & Discovery ◽

10.2174/1570180817999200421144007 ◽

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.

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In Situ Vitrification of Lung Cancer Organoids on a Microwell Array

Micromachines ◽

10.3390/mi12060624 ◽

2021 ◽

Vol 12 (6) ◽

pp. 624

Author(s):

Qiang Liu ◽

Tian Zhao ◽

Xianning Wang ◽

Zhongyao Chen ◽

Yawei Hu ◽

...

Keyword(s):

Lung Cancer ◽

Drug Sensitivity ◽

Simple Procedure ◽

Three Dimensional ◽

Cancer Drug ◽

Microwell Array ◽

Sensitivity Tests ◽

Anti Cancer

Three-dimensional cultured patient-derived cancer organoids (PDOs) represent a powerful tool for anti-cancer drug development due to their similarity to the in vivo tumor tissues. However, the culture and manipulation of PDOs is more difficult than 2D cultured cell lines due to the presence of the culture matrix and the 3D feature of the organoids. In our other study, we established a method for lung cancer organoid (LCO)-based drug sensitivity tests on the superhydrophobic microwell array chip (SMAR-chip). Here, we describe a novel in situ cryopreservation technology on the SMAR-chip to preserve the viability of the organoids for future drug sensitivity tests. We compared two cryopreservation approaches (slow freezing and vitrification) and demonstrated that vitrification performed better at preserving the viability of LCOs. Next, we developed a simple procedure for in situ cryopreservation and thawing of the LCOs on the SMAR-chip. We proved that the on-chip cryopreserved organoids can be recovered successfully and, more importantly, showing similar responses to anti-cancer drugs as the unfrozen controls. This in situ vitrification technology eliminated the harvesting and centrifugation steps in conventional cryopreservation, making the whole freeze–thaw process easier to perform and the preserved LCOs ready to be used for the subsequent drug sensitivity test.

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

Inquiry@Queen's Undergraduate Research Conference Proceedings ◽

10.24908/iqurcp.8940 ◽

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

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Surfactant-Based Anhydrous Nano Carrier System for Poorly Aqueous Soluble Anti-Cancer Drugs

Handbook of Research on Advancements in Cancer Therapeutics - Advances in Medical Diagnosis, Treatment, and Care ◽

10.4018/978-1-7998-6530-8.ch014 ◽

2021 ◽

pp. 413-432

Author(s):

Shekhar Verma ◽

Nagendra Chandrawanshi ◽

Vishal Jain

Keyword(s):

Controlled Release ◽

Primary Objective ◽

Water Soluble ◽

Cancer Drug ◽

Cancer Drugs ◽

Carrier System ◽

Anti Cancer ◽

New Chemical Entities ◽

Poorly Water Soluble ◽

Nano Emulsion

Around 40% of new chemical entities and drugs are lipophilic or poor aqueous soluble in nature. Among them many anti-cancer drugs are also consist lipophilic properties. Available poorly water soluble anti-cancer drugs are paclitaxel, etoposide, and docetaxel. To get better stability of those anti-cancer drug via encapsulation and searching suitable carrier system for the controlled release, design and development requires of anhydrous nano carrier system. However, to deliver and entrapment of these kind of anti-cancer drugs are very essential with avoidance of water free preparation to get suitable controlled release application and achieve targeting site. The primary objective of proposed chapter is to develop and design novel stable anhydrous or non-aqueous nano emulsion carrier system and provide suitable carrier system for poorly aqueous soluble anti-cancer drugs. Another important aim is to design and develop better stabilizing agent by combining different type of surfactant, co-surfactant, and co-solvent.

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Andrographolide, A Natural Antioxidant: An Update

Antioxidants ◽

10.3390/antiox8120571 ◽

2019 ◽

Vol 8 (12) ◽

pp. 571 ◽

Cited By ~ 12

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.

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