Fluorescent Polyelectrolyte System to Track Anthocyanins Delivery inside Melanoma Cells

Over the past decades, there has been a growing interest in using natural molecules with therapeutic potential for biomedical applications. In this context, our aim is focused on anthocyanins (AN) as molecules with anticancer properties that could be used in melanoma local therapies. Due to their susceptibility to environmental changes, current study is based on the design and development of a fluorescent system for carrying and trafficking AN inside melanoma cells. The architectural structure of the proposed system CaCO3(PAH)@RBITC@AN reflects a spherical shape, 1080 nm diameter and a solid groundwork CaCO3(PAH), on which rhodamine B isothiocyanate (RBITC) fluorophore was firstly added; then, poly(acrylic acid) (PAA) polyelectrolytes and poly(allylamine hydrochloride) (PAH) were successfully deposited. Purified AN from chokeberries were entrapped between PAA layers (rate of 94.6%). In vitro tests confirmed that CaCO3(PAH)@RBITC@AN does not affect the proliferation of melanoma B16-F10 cells and proved that their internalization and trafficking can be followed after 24 h of treatment. Data presented here could contribute not only to the existing knowledge about the encapsulation technology of AN but also might bring relevant information for a novel formula to deliver therapeutic molecules or other bio-imaging agents directly into melanoma cells, a strategy that could positively improve tumor therapies.

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A Review of Saurauia roxburghii Wall. (Actinidiacaea) as a Traditional Medicinal Plant, Its Phytochemical Study and Therapeutic Potential

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200709175138 ◽

2020 ◽

Vol 20 (19) ◽

pp. 2036-2051

Author(s):

Afsana Nahrin ◽

Md. Junaid ◽

Syeda Samira Afrose ◽

Muhammad Shaiful Alam ◽

S.M. Zahid Hosen ◽

...

Keyword(s):

Ursolic Acid ◽

Therapeutic Potential ◽

Wide Spectrum ◽

Relevant Information ◽

In Vitro Tests ◽

Pharmacological Activities ◽

Phytochemical Study ◽

Corosolic Acid

Saurauia roxburghii Wall. is an interesting plant, found growing chiefly along the eastern and south-eastern countries of Asia. The various ethnic groups of these regions use the plant as a medication for relieving a wide spectrum of diseases and conditions, including indigestion, boils, fever, gout, piles, eczema, asthma, ulcers, bronchitis, epilepsy, and hepatitis B. This review aims to appraise the vernacular information, botanical characterization, geographical distribution, traditional uses, phytochemistry, and pharmacological activities of S. roxburghii as well as to conduct a critical analysis on the findings. To understand the therapeutic potential and provide an overall idea about the ethnomedicinal practices, phytochemistry, and pharmacological activities of S. roxburghii, relevant information was collected via a library and electronic search of online journals, books, and reputed databases. Phytochemical examination revealed the presence of alkaloids, glycosides, O-glycosides, flavonoids, carbohydrates, saponins, steroids, reducing sugars, tannins, phlobatannins, and triterpenoids. The sterols were identified as Stigmasterol and beta-Sitosterol. The triterpenes were found to be Ursolic acid, Corosolic acid, Maslinic acid, 24-Hydroxy corosolic acid, 3b,7b,24-trihydroxy-urs-12-en-28-oic acid, Oleanolic acid, beta-Amyrin, cis-3-O-p-Hydroxycinnamoyl ursolic acid, trans-3-O-p- Hydroxycinnamoyl ursolic acid, and 7,24-dihydroxyursolic acid. Several in-vivo and in-vitro tests revealed anti-bacterial, anti-cancer, anti-diabetic, anti-oxidant, and anti-viral activities of the plant leaves. Detailed analysis of the information collected on S. roxburghii suggested some promising leads for future drug development. However, many scientific gaps were found in the study of this and further extensive investigation is needed to fully understand the mechanism of action of the active constituents and exploit its therapeutic promises.

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Natural products with therapeutic potential in melanoma metastasis

Natural Product Reports ◽

10.1039/c4np00130c ◽

2015 ◽

Vol 32 (8) ◽

pp. 1170-1182 ◽

Cited By ~ 41

Author(s):

A. AlQathama ◽

J. M. Prieto

Keyword(s):

Natural Products ◽

Cancer Treatment ◽

Therapeutic Potential ◽

Melanoma Cells ◽

Mechanisms Of Action ◽

Melanoma Metastasis ◽

Pharmacological Effects ◽

Cytotoxic Compounds

Natural products continue to provide lead cytotoxic compounds for cancer treatment but less attention has been given to antimigratory compounds. We here systematically and critically survey more than 30 natural products with direct in vitro and in vivo pharmacological effects on migration and/or metastasis of melanoma cells and chart the mechanisms of action for this underexploited property.

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Capsaicin Exerts Therapeutic Effects by targeting tNOX-SIRT1 Axis and Augmenting ROS-Dependent Cytotoxic Autophagy in Melanoma Cancer Cells

10.21203/rs.3.rs-117713/v1 ◽

2020 ◽

Author(s):

Atikul Islam ◽

Pei-Fang Hsieh ◽

Jou-Chun Chou ◽

Jiunn-Wang Liao ◽

Ming-Kun Hsieh ◽

...

Keyword(s):

Malignant Melanoma ◽

Cancer Cells ◽

Nadh Oxidase ◽

Treatment Options ◽

Melanoma Cells ◽

Therapeutic Effects ◽

Melanoma Cancer ◽

Anticancer Properties

Abstract Background: Although considered a rare form of skin cancer, malignant melanoma has steadily increased internationally and is a main cause of cancer-associated death worldwide. The treatment options for malignant melanoma are very limited. Accumulating data suggest that the natural compound, capsaicin, exhibits preferential anticancer properties to act as a nutraceutical agent. Here, we explored the underlying molecular events involved in the inhibitory effects of capsaicin on the growth of melanoma cells.Methods: The cellular thermal shift assay (CETSA) and isothermal dose response fingerprint (ITDRFCETSA) were utilized to validate the binding of capsaicin with the tumor-associated NADH oxidase, tNOX (ENOX2) in melanoma cells. We also assessed the cellular impact of capsaicin-targeting of tNOX on A375 cells by flow cytometry and protein analysis. The essential role of tNOX in tumor- and melanoma-growth limiting abilities of capsaicin was evaluated in C57BL/6 mice.Results: Our data show that capsaicin directly targets cellular tNOX to inhibit its enzymatic activity and enhance protein degradation capacity. The inhibition of tNOX by capsaicin is accompanied by the attenuation of SIRT1, a NAD+-dependent deacetylase that enhances ULK1 acetylation to induce ROS-dependent autophagy in melanoma cells. Capsaicin treatment of mice implanted with melanoma cancer cells suppressed tumor growth by down-regulating tNOX and SIRT1, which was also seen in an in vivo xenograft study with tNOX-depleted melanoma cells. Conclusions: Together, our findings suggest that tNOX expression is important for the growth of melanoma cancer cells both in vitro and in vivo, and that inhibition of the tNOX-SIRT1 axis contributes to inducting cytotoxic ROS-dependent autophagy in melanoma cells.

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Review of Ethnomedicinal, Phytochemical and Pharmacological Properties of Lannea schweinfurthii (Engl.) Engl.

Molecules ◽

10.3390/molecules24040732 ◽

2019 ◽

Vol 24 (4) ◽

pp. 732 ◽

Cited By ~ 1

Author(s):

Alfred Maroyi

Keyword(s):

Animal Studies ◽

Therapeutic Potential ◽

American Chemical Society ◽

Relevant Information ◽

Chemical Society ◽

Pharmacological Properties ◽

Phytochemical Compounds ◽

Cytotoxicity Activities ◽

Ethnomedicinal Uses

Lannea schweinfurthii is a valuable medicinal plant species among different ethnic groups in tropical Africa. The aim of the current study was to review existing literature on the ethnomedicinal uses, phytochemistry and pharmacological properties of L. schweinfurthii in an effort to evaluate the therapeutic potential of the species. The relevant information on the ethnomedicinal uses, phytochemistry and pharmacological properties of L. schweinfurthii was generated from several sources including books, book chapters, theses, scientific reports and journal articles obtained from the library and internet sources such as SciFinder, Wiley, Web of Science, American Chemical Society publications, PubMed, BMC, Elsevier, Science Direct, Scielo and Scopus. Traditionally, L. schweinfurthii is used against reproductive system disorders, respiratory disorders, injuries, headache, blood system disorders, infections or infestations and gastro-intestinal disorders. The phytochemical compounds that have been isolated from L. schweinfurthii include alkaloids, anthocyanins, flavonoids, glycosides, phenols, saponins, steroids, tannins and terpenoids. The in vitro and animal studies carried out so far from the crude extracts and compounds isolated from the species exhibited acetylcholinesterase inhibitory, anti-apoptotic, antibacterial, antiviral, anti-giardial, anti-inflammatory, antioxidant, antiplasmodial, antitrypanosomal, hepatoprotective, larvicidal and cytotoxicity activities. Detailed ethnopharmacological studies emphasizing clinical and toxicological evaluations are needed to assess efficacy and safety of the species as herbal medicine.

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Prodigiosin Modulates the Immune Response and Could Promote a Stable Atherosclerotic Lession in C57bl/6 Ldlr-/- Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21176417 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6417 ◽

Cited By ~ 1

Author(s):

Alejandro Cuevas ◽

Nicolás Saavedra ◽

Luis A. Salazar ◽

Marcela F. Cavalcante ◽

Jacqueline C. Silva ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Atherosclerotic Plaque ◽

Therapeutic Potential ◽

Inflammatory Marker ◽

Interleukin 2 ◽

Atheromatous Plaque ◽

In Vitro Tests ◽

Significant Difference

Atherosclerosis is a chronic inflammatory disease, whose progression and stability are modulated, among other factors, by an innate and adaptive immune response. Prodiginines are bacterial secondary metabolites with antiproliferative and immunomodulatory activities; however, their effect on the progression or vulnerability of atheromatous plaque has not been evaluated. This study assessed the therapeutic potential of prodigiosin and undecylprodigiosin on inflammatory marker expression and atherosclerosis. An in vitro and in vivo study was carried out. Migration, low-density lipoprotein (LDL) uptake and angiogenesis assays were performed on cell types involved in the pathophysiology of atherosclerosis. In addition, male LDL receptor null (Ldlr-/-) C57BL/6J mice were treated with prodigiosin or undecylprodigiosin for 28 days. Morphometric analysis of atherosclerotic plaques, gene expression of atherogenic factors in the aortic sinus and serum cytokine quantification were performed. The treatments applied had slight effects on the in vitro tests performed, highlighting the inhibitory effect on the migration of SMCs (smooth muscle cells). On the other hand, although no significant difference in atherosclerotic plaque progression was observed, gene expression of IL-4 and chemokine (C-C motif) ligand 2 (Ccl2) was downregulated. In addition, 50 µg/Kg/day of both treatments was sufficient to inhibit circulating tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in serum. These results suggested that prodigiosin and undecylprodigiosin modulated inflammatory markers and could have an impact in reducing atherosclerotic plaque vulnerability.

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Design andIn VitroEvaluation of a New Nano-Microparticulate System for Enhanced Aqueous-Phase Solubility of Curcumin

BioMed Research International ◽

10.1155/2013/724763 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 18

Author(s):

Diana Guzman-Villanueva ◽

Ibrahim M. El-Sherbiny ◽

Dea Herrera-Ruiz ◽

Hugh D. C. Smyth

Keyword(s):

Therapeutic Potential ◽

Curcuma Longa ◽

Aqueous Solubility ◽

Release Profile ◽

Free Form ◽

Phase Solubility ◽

Ionotropic Gelation ◽

Anticancer Properties ◽

Freeze Dried

Curcumin, a yellow polyphenol derived from the turmericCurcuma longa, has been associated with a diverse therapeutic potential including anti-inflammatory, antioxidant, antiviral, and anticancer properties. However, the poor aqueous solubility and low bioavailability of curcumin have limited its potential when administrated orally. In this study, curcumin was encapsulated in a series of novel nano-microparticulate systems developed to improve its aqueous solubility and stability. The nano-microparticulate systems are based entirely on biocompatible, biodegradable, and edible polymers including chitosan, alginate, and carrageenan. The particles were synthesized via ionotropic gelation. Encapsulating the curcumin into the hydrogel nanoparticles yielded a homogenous curcumin dispersion in aqueous solution compared to the free form of curcumin. Also, thein vitrorelease profile showed up to 95% release of curcumin from the developed nano-microparticulate systems after 9 hours in PBS at pH 7.4 when freeze-dried particles were used.

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A review on chemistry, source and therapeutic potential of lambertianic acid

Zeitschrift für Naturforschung C ◽

10.1515/znc-2020-0267 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Md Shahinozzaman ◽

Moutushi Islam ◽

Bristy Basak ◽

Arifa Sultana ◽

Rashiduzzaman Emran ◽

...

Keyword(s):

Molecular Mechanisms ◽

Therapeutic Potential ◽

Bioactive Compound ◽

Cancer Cell Proliferation ◽

Neuroprotective Effects ◽

Potential Health ◽

Anticancer Properties ◽

Toxicological Profile ◽

Lambertianic Acid

Abstract Lambertianic acid (LA) is a diterpene bioactive compound mainly purified from different species of Pinus. It is an optical isomer of another natural compound daniellic acid and was firstly purified from Pinus lambertiana. LA can be synthesized in laboratory from podocarpic acid. It has been reported to have potential health benefits in attenuating obesity, allergies and different cancers including breast, liver, lung and prostate cancer. It exhibits anticancer properties through inhibiting cancer cell proliferation and survival, and inducing apoptosis, targeting major signalling components including AKT, AMPK, NFkB, COX-2, STAT3, etc. Most of the studies with LA were done using in vitro models, thus warranting future investigations with animal models to evaluate its pharmacological effects such as antidiabetic, anti-inflammatory and neuroprotective effects as well as to explore the underlying molecular mechanisms and toxicological profile. This review describes the chemistry, source, purification and therapeutic potentials of LA and it can therefore be a suitable guideline for any future study with LA.

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Isolation and Study of Bacteriophages Specific Against Multidrug Resistant Salmonella spp. and Assessment of their Therapeutic Potential

MODERN ISSUES OF MEDICINE AND MANAGEMENT ◽

10.52340/mid.2021.641 ◽

2021 ◽

Author(s):

Khatuna Makalatia ◽

Elene Kakabadze ◽

Nino Grdzelishvili ◽

Nata Bakuradze ◽

Nino Chanishvili

Keyword(s):

Therapeutic Potential ◽

Multidrug Resistant ◽

In Vitro Tests ◽

Salmonella Spp ◽

Clinical Strains ◽

Additional Tool ◽

Salmonella Infections ◽

Microbiological Methods ◽

Genetic Features

Within the scope of the study, clinical non-typhoidal Salmonella were isolated in Armenia and Georgia and identified based on conventional microbiological methods and MALDI-TOF MS. These isolates were further analysed by serotyping (White-Kauffmann-Le Minor scheme) and their antimicrobial susceptibility profiles were defined. A total of 40 antibiotic resistance profiles were identified, of which 35 were characteristic of clinical strains. Out of a total of 345 isolates, 238 strains from Georgia, Armenia and Ireland were eventually selected for our study.Using the strains of this collection, 13 new bacteriophages were isolated, characterized by biological and genetic features. Based on the data obtained, phages were classified and the peculiarities of their life cycle were determined (virulent-lytic, moderate-lysogenic).Analysis of the sequencing results showed that only one of the 12 phages identified as temperate phage (vB_GEC_ TR), it belongs to the family Podoviridae, genus-Laderbergvirus. While the other 11 phages are virulent, they are related to well-known and characterized phages, which are used in various phage preparations. Analysis of their genomes did not show any lysogeny associated genes. Among the virulent phages, 6 are members of Myoviridae family (vB_GEC_B1, vB_GEC_B3, vB_GEC_MG, vB_GEC_BS, vB_GEC_NS7, vB_GEC_7A) and 5 of the Syphoviridae family (vB_GEC_N5, vB_GEC_N8, vB_GEC_M4, vB_GEC_M5, vB_GEC_Hi). In vitro tests revealed that the phages - vB_GEC_B1, vB_GEC_BS, vB_GEC_B3, vB_GEC_NS7, vB-GEC-N8 showed high activity (60% to 80%) against the examined strains. The phages have been shown to be more effective against clinical strains (≈90%) than against veterinary strains (≈70%). The strains susceptible to these phages were mainly S.typhimurium and S. Enteritidis serovars and are largely of clinical origin. Based on our research we can conclude that the application of phages as an additional tool for the treatment of MDR Salmonella infections seems to be plausible. Phages are natural and specific antibacterial agents, which can lyse bacteria.irrespective of their AMR status, whilst leaving the commensal microflora unharmed. This is one of the main advantages of phages in comparison to antibiotics. The phages tested in this study showed potential for application in phage therapy against MDR Salmonella infections.

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The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells

Cancers ◽

10.3390/cancers12102936 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2936

Author(s):

You-Cheng Hseu ◽

Yu-Chi Chiang ◽

Yugandhar Vudhya Gowrisankar ◽

Kai-Yuan Lin ◽

Sheng-Teng Huang ◽

...

Keyword(s):

Cell Death ◽

Nude Mice ◽

Melanoma Cell Line ◽

Caspase 3 ◽

Melanoma Cells ◽

Human Melanoma ◽

Autophagic Cell Death ◽

Anticancer Properties

Melanoma is the most prevalent type of skin cancer with high mortality rates. This study demonstrates the in vitro and in vivo anticancer properties of chalcone flavokawain B (FKB) induced ROS-mediated apoptosis and autophagy in human melanoma (human epithelial melanoma cell line A375 and/or human skin lymph node derived melanoma cell line A2058) cells. Cell viability was calculated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the expression patterns of various apoptosis, autophagy-associated proteins were determined by Western blot methods. Annexin V was detected by flow cytometry, whereas acidic vesicular organelles (AVOs) and intracellular ROS levels were measured by fluorescence microscopy. The in vivo anticancer properties of FKB were evaluated by xenografting the A375 cells into nude mice. The results convey that FKB inhibited cell viability, B-Raf proto-oncogene, serine/threonine kinase (BRAF)/extracellular signal-regulated kinase (ERK) expression in human melanoma cells. Caspase-3 activation, poly (ADP-ribose) polymerase (PARP) cleavage pathway, and Bcl2 associated X (Bax)/B-cell lymphoma 2 (Bcl-2) dysregulation were involved in the execution of apoptosis. Moreover, FKB-induced autophagy was observed through increased microtubule-associated protein 1A/1B-light chain 3B (LC3-II) accumulation and AVOs formation, which was also associated with an increase in sequestosome 1 (SQSTM1/p62), decreased protein kinase B (AKT)/mammalian target of rapamycin (mTOR) expressions, and dysregulated Beclin-1/Bcl-2 levels. Autophagy inhibitors [3-methyladenine (3-MA)/chloroquine (CQ)] and LC3 silencing suppressed FKB-induced apoptosis by decreasing caspase-3 in melanoma cells. The antioxidant N-acetylcysteine (NAC) diminished FKB-induced apoptotic and autophagic cell death. However, the inhibition of apoptosis decreased FKB-induced autophagy (LC3-I/II). The in vivo study confirmed that FKB inhibited melanoma growth in A375-xenografted nude mice. This study concluded that FKB is critically associated with the execution and generation of ROS-modulated apoptotic and autophagic cell death of melanoma cells. FKB also repressed tumor growth in xenografted nude mice. Therefore, flavokawain B might be a potential anti-tumor agent in human melanoma treatment.

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STUDY OF ENHANCED ANTI-INFLAMMATORY POTENTIAL OF NIGELLA SATIVA IN TOPICAL NANOFORMULATION

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i7.22966 ◽

2018 ◽

Vol 10 (7) ◽

pp. 41 ◽

Cited By ~ 3

Author(s):

Faisal Obaid Alotaibi ◽

Gulam Mustafa ◽

Alka Ahuja

Keyword(s):

Zeta Potential ◽

Size Distribution ◽

Therapeutic Potential ◽

Ex Vivo ◽

Nigella Sativa ◽

In Vitro Release ◽

Spherical Shape ◽

Active Constituent ◽

Anti Inflammatory

Objective: Formulate a nanocarrier for enhancing the anti-inflammatory activity of thymoquinone (Tq), a major active constituent of Nigella sativa.Methods: Nanoformulation of Tq was developed by low energy emulsification techniques. NanoTqs were pre-screened by different thermodynamic stability tests, followed by in vitro release, zeta potential, viscosity, the transmittance (%), globule size distribution and ex vivo studies. The morphology of the optimized NanoTq was determined by transmission electron microscopy (TEM) which revealed fairly spherical shape and good correlation with particle size distribution study. The formulation used for assessment of the anti-inflammatory potential and permeability enhancement contained mixture of essential oil of Nigella sativa: Capryol 90 (3:7, 10%, v/v), Tween 80 (21.75%, v/v), PEG 400 (7.25%, v/v) and double distilled water (61%, v/v).Results: The in vitro permeation of Tq from optimized formulations was found extremely significant (p<0.001) in comparison to apiTq. The steady state flux (Jss), the permeability coefficient (Kp) and enhancement ratio (Er) of NanoTq gel was determined and compared with apiTq. The comparative anti-inflammatory effects of the optimized formulations NanoTq, apiTq and DicloGel was assessed on the edema in the carrageenan-induced paw model in Wistar rats. Therapeutic potential of NanoTq was found statistically extremely significant (P<0.0001) compared to apiTq and insignificant comparable with standard DicloGel. Storage stability of NanoTq showed insignificant changes in the zeta potential, droplet size and was free from any physical instability.Conclusion: The optimized nano formulation with a lower dose of Tq showed better anti-inflammatory effects, indicating greater absorption capability through the stratum corneum.

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