The Trail, 1939-12-15

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Melanin and Melanin-Functionalized Nanoparticles as Promising Tools in Cancer Research—A Review

Cancer poses an ongoing global challenge, despite the substantial progress made in the prevention, diagnosis, and treatment of the disease. The existing therapeutic methods remain limited by undesirable outcomes such as systemic toxicity and lack of specificity or long-term efficacy, although innovative alternatives are being continuously investigated. By offering a means for the targeted delivery of therapeutics, nanotechnology (NT) has emerged as a state-of-the-art solution for augmenting the efficiency of currently available cancer therapies while combating their drawbacks. Melanin, a polymeric pigment of natural origin that is widely spread among many living organisms, became a promising candidate for NT-based cancer treatment owing to its unique physicochemical properties (e.g., high biocompatibility, redox behavior, light absorption, chelating ability) and innate antioxidant, photoprotective, anti-inflammatory, and antitumor effects. The latest research on melanin and melanin-like nanoparticles has extended considerably on many fronts, allowing not only efficient cancer treatments via both traditional and modern methods, but also early disease detection and diagnosis. The current paper provides an updated insight into the applicability of melanin in cancer therapy as antitumor agent, molecular target, and delivery nanoplatform

Melanin and Melanin-Functionalized Nanoparticles as Promising Tools in Cancer Research—A Review

Cancer poses an ongoing global challenge, despite the substantial progress made in the prevention, diagnosis, and treatment of the disease. The existing therapeutic methods remain limited by undesirable outcomes such as systemic toxicity and lack of specificity or long-term efficacy, although innovative alternatives are being continuously investigated. By offering a means for the targeted delivery of therapeutics, nanotechnology (NT) has emerged as a state-of-the-art solution for augmenting the efficiency of currently available cancer therapies while combating their drawbacks. Melanin, a polymeric pigment of natural origin that is widely spread among many living organisms, became a promising candidate for NT-based cancer treatment owing to its unique physicochemical properties (e.g., high biocompatibility, redox behavior, light absorption, chelating ability) and innate antioxidant, photoprotective, anti-inflammatory, and antitumor effects. The latest research on melanin and melanin-like nanoparticles has extended considerably on many fronts, allowing not only efficient cancer treatments via both traditional and modern methods, but also early disease detection and diagnosis. The current paper provides an updated insight into the applicability of melanin in cancer therapy as antitumor agent, molecular target, and delivery nanoplatform

Photodegradation of bexarotene and its implication for cytotoxicity

A detailed understanding of the stability of an active pharmaceutical ingredient and a pharmaceutical dosage form is essential for the drug-development process and for safe and effective use of medicines. Photostability testing as an inherent part of stability studies provides valuable knowledge on degradation pathways and structures of products generated under UV irradiation. Photostability is particularly important for topically administered drugs, as they are more exposed to UV radiation. Bexarotene is a more recent third-generation retinoid approved by the U.S. Food and Drug Administration and the European Medicines Agency as a topically applied anticancer agent. The present study aimed to assess bexarotene photostability, including the presence of UV filters, which have been permitted to be used in cosmetic products in Europe and the USA. The bexarotene photostability testing was performed in ethanol solutions and in formulations applied on PMMA plates. The UPLC-MS/MS technique was used to determine the tested substance. The presence of photocatalysts such as TiO2 or ZnO, as well as the organic UV filters avobenzone, benzophenone-3, meradimate, and homosalate, could contribute to degradation of bexarotene under UV irradiation. Four photocatalytic degradation products of bexarotene were identified for the first time. The antiproliferative properties of the degradation products of bexarotene were assessed by MTT assay on a panel of human adherent cancer cells, and concentration-dependent growth inhibition was evidenced on all tested cell lines. The cytotoxicity of the formed products after 4 h of UV irradiation was significantly higher than that of the parent compound (p < 0.05). Furthermore non-cancerous murine fibroblasts exhibited marked concentration-dependent inhibition by bexarotene, while the degradation products elicited more pronounced antiproliferative action only at the highest applied concentration

Botanical Therapeutics: Phytochemical Screening and Biological Assessment of Chamomile, Parsley and Celery Extracts against A375 Human Melanoma and Dendritic Cells

Chamomile, parsley, and celery represent major botanical sources of apigenin, a well-known flavone with chemopreventive properties. The aim of this study was to assess the phytochemical composition, antioxidant, and anti-inflammatory potential of methanol extracts obtained from chamomile, parsley, and celery collected from Romania, as well as the biological activity against A375 human melanoma and human dendritic cells. Results have shown that all three extracts are rich in polyphenolic compounds and flavonoids, and they generate a radical scavenger capacity, iron chelation potential, as well as lipoxygenase inhibition capacity. Chamomile and celery extracts present weak antiproliferative and pro-apoptotic properties in the set experimental conditions, while parsley extract draws out significant pro-apoptotic potential against A375 human melanoma cells. Parsley and chamomile extracts affected the fibroblast-like morphology of the screened tumor cell line. On the other hand, chamomile and celery extracts abrogated the expansion of LPS-activated dendritic cells, while the metabolic activity was attenuated by stimulation with celery extract; chamomile and parsley extracts had no effect upon this parameter. Chamomile and parsley extracts incubation with naive dendritic cells did not trigger cytokine secretion (TNF-alpha, IL-6, IL-10), but celery extract stimulation significantly reduced the anti-inflammatory, cytokine IL-10

Germinated and Ungerminated Seeds Extract from Two Lupinus Species: Biological Compounds Characterization and In Vitro and In Vivo Evaluations

In recent years, nutraceuticals attracted a great amount of attention in the biomedical research due to their significant contribution as natural agents for prevention of various health issues. Ethanolic extracts from the ungerminated and germinated seeds of Lupinus albus L. and Lupinus angustifolius L. were analyzed for the content in isoflavones (genistein) and cinnamic acid derivatives. Additionally, the extracts were evaluated for antimicrobial, antiproliferative, and anti-inflammatory properties, using in vitro and in vivo tests. Germination proved to be a method of choice in increasing the amount of genistein and cinnamic acid derivatives in both Lupinus albus L. and Lupinus angustifolius L. seeds. Biological evaluation of all vegetal extracts revealed a weak therapeutic potential for both ungerminated and germinated seeds

Botanical therapeutics : phytochemical screening and biological assessment of chamomile, parsley and celery extracts against A375 human melanoma and dendritic cells

Chamomile, parsley, and celery represent major botanical sources of apigenin, a well-known flavone with chemopreventive properties. The aim of this study was to assess the phytochemical composition, antioxidant, and anti-inflammatory potential of methanol extracts obtained from chamomile, parsley, and celery collected from Romania, as well as the biological activity against A375 human melanoma and human dendritic cells. Results have shown that all three extracts are rich in polyphenolic compounds and flavonoids, and they generate a radical scavenger capacity, iron chelation potential, as well as lipoxygenase inhibition capacity. Chamomile and celery extracts present weak antiproliferative and pro-apoptotic properties in the set experimental conditions, while parsley extract draws out significant pro-apoptotic potential against A375 human melanoma cells. Parsley and chamomile extracts affected the fibroblast-like morphology of the screened tumor cell line. On the other hand, chamomile and celery extracts abrogated the expansion of LPS-activated dendritic cells, while the metabolic activity was attenuated by stimulation with celery extract; chamomile and parsley extracts had no effect upon this parameter. Chamomile and parsley extracts incubation with naive dendritic cells did not trigger cytokine secretion (TNF-alpha, IL-6, IL-10), but celery extract stimulation significantly reduced the anti-inflammatory, cytokine IL-10

A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phytocompound

Apigenin (4&#8242;,5,7-trihydroxyflavone) (Api) is an important component of the human diet, being distributed in a wide number of fruits, vegetables and herbs with the most important sources being represented by chamomile, celery, celeriac and parsley. This study was designed for a comprehensive evaluation of Api as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound. In the set experimental conditions, Api presents antiproliferative activity against the A375 human melanoma cell line, a G2/M arrest of the cell cycle and cytotoxic events as revealed by the lactate dehydrogenase release. Caspase 3 activity was inversely proportional to the Api tested doses, namely 30 &#956;M and 60 &#956;M. Phenomena of early apoptosis, late apoptosis and necrosis following incubation with Api were detected by Annexin V-PI double staining. The flavone interfered with the mitochondrial respiration by modulating both glycolytic and mitochondrial pathways for ATP production. The metabolic activity of human dendritic cells (DCs) under LPS-activation was clearly attenuated by stimulation with high concentrations of Api. Il-6 and IL-10 secretion was almost completely blocked while TNF alpha secretion was reduced by about 60%. Api elicited antiangiogenic properties in a dose-dependent manner. Both concentrations of Api influenced tumour cell growth and migration, inducing a limited tumour area inside the application ring, associated with a low number of capillaries