scholarly journals Preclinical development of a novel CD47 nanobody with less toxicity and enhanced anti-cancer therapeutic potential

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Linlin Ma ◽  
Min Zhu ◽  
Junwei Gai ◽  
Guanghui Li ◽  
Qing Chang ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Preclinical Development ◽  
Anti Cancer

Phytochemical, Pharmacological Activities and Ayurvedic Significances of Magical Plant Mimosa pudica Linn

2020 ◽  
Vol 17 ◽  
Author(s):  
Vijay Kumar
Keyword(s):  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Chemical Constituents ◽  
Future Research ◽  
Mimosa Pudica ◽  
Pharmacological Activities ◽  
Medicinal Uses ◽  
Traditional Medicines ◽  
Crude Extracts ◽  
Anti Cancer

: Mimosa pudica Linn is an integrated part of Traditional Medicines Systems of India, China, Africa, Korea and America. It has been used from centuries in traditional medicines to cure different diseases like fever, diabetes, constipation, jaundice, ulcers, biliousness, and dyspepsia. It is an important ingredient of wide class of herbal formulations. To assess the scientific evidence for therapeutic potential of Mimosa pudica Linn and to identify the gaps for future research. The available information on the ethno-medicinal uses, phytochemistry, pharmacology and toxicology of Mimosa pudica Linn was collected via a library and electronic searches in Sci-Finder, Pub-Med, Science Direct, Google Scholar for the period, 1990 to 2020. In traditional medicinal systems, variety of ethno-medicinal applications of Mimosa pudica Linn has been noticed. Phytochemical investigation has resulted in identification of 40 well known chemical constituents, among which alkaloids, phenols and flavionoids are the predominant groups. The crude extracts and isolates have exhibited a wide spectrum of in vitro and in vivo pharmacological activities including anti-cancer, anti-inflammation, osteoporosis, neurological disorders, hypertension etc.. To quantify the Mimosa pudica Linn and its formulations, analytical techniques like HPLC and HPTLC has shown dominancy with good range of recovery and detection limit. Mimosa pudica Linn is the well-known herb since an ancient time. The pharmacological results supported some of the applications of Mimosa pudica Linn in traditional medicine systems. Perhaps, the predominance of alkaloids, phenols and flavionoids are responsible for the pharmacological activities the crude extracts and isolates of Mimosa pudica Linn. Further, there is need to isolate and evaluate the active chemical constituents of Mimosa pudica Linn having significant medicinal values. In future, it is important to study the exact mechanism associated with the phytochemicals of Mimosa pudica Linn especially on anti-cancer activities. Notably, toxicity studies on Mimosa pudica Linn are limited which are to be explored in future for the safe application of Mimosa pudica Linn and its formulations.

scholarly journals The HGR motif is the antiangiogenic determinant of vasoinhibin: implications for a therapeutic orally active oligopeptide

Angiogenesis ◽  
2021 ◽  
Author(s):  
Juan Pablo Robles ◽  
Magdalena Zamora ◽  
Lourdes Siqueiros-Marquez ◽  
Elva Adan-Castro ◽  
Gabriela Ramirez-Hernandez ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Clinical Evidence ◽  
Therapeutic Potential ◽  
Peripartum Cardiomyopathy ◽  
Loss Of Function ◽  
Functional Determinant ◽  
Melanoma Tumor ◽  
Linear Motif ◽  
Anti Cancer ◽  
Orally Active

AbstractThe hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as a therapeutic agent by showing that a short linear motif of just three residues (His46-Gly47-Arg48) (HGR) is the functional determinant of vasoinhibin. The HGR motif is conserved throughout evolution, its mutation led to vasoinhibin loss of function, and oligopeptides containing this sequence inhibited angiogenesis and vasopermeability with the same potency as whole vasoinhibin. Furthermore, the oral administration of an optimized cyclic retro-inverse vasoinhibin heptapeptide containing HGR inhibited melanoma tumor growth and vascularization in mice and exhibited equal or higher antiangiogenic potency than other antiangiogenic molecules currently used as anti-cancer drugs in the clinic. Finally, by unveiling the mechanism that obscures the HGR motif in prolactin, we anticipate the development of vasoinhibin-specific antibodies to solve the on-going challenge of measuring endogenous vasoinhibin levels for diagnostic and interventional purposes, the design of vasoinhibin antagonists for managing insufficient angiogenesis, and the identification of putative therapeutic proteins containing HGR.

scholarly journals Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

2021 ◽  
Vol 22 (7) ◽  
pp. 3755
Author(s):  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Artur Beberok ◽  
...  
Keyword(s):  
Uv Radiation ◽  
Therapeutic Potential ◽  
Melanin Synthesis ◽  
Uvb Radiation ◽  
Biochemical Basis ◽  
Skin Hyperpigmentation ◽  
Human Melanocytes ◽  
Anti Cancer ◽  
Normal Human

Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.

scholarly journals Dietary Curcumin: Correlation between Bioavailability and Health Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2147 ◽  
Author(s):  
Michele Dei Cas ◽  
Riccardo Ghidoni
Keyword(s):  
Small Intestine ◽  
Cellular Uptake ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Pharmacokinetic Profile ◽  
Yellow Pigment ◽  
The Body ◽  
Anti Cancer ◽  
Poor Absorption ◽  
Oral Delivery Systems

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

scholarly journals Development of Small-Molecule STING Activators for Cancer Immunotherapy

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 33
Author(s):  
Hee Ra Jung ◽  
Seongman Jo ◽  
Min Jae Jeon ◽  
Hyelim Lee ◽  
Yeonjeong Chu ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Cyclic Gmp ◽  
Therapeutic Potential ◽  
Interferon Response ◽  
Type I ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Sting Pathway

In cancer immunotherapy, the cyclic GMP–AMP synthase–stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from ‘cold’ to ‘hot’ through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity. Furthermore, KAS-08 was validated as an effective STING pathway activator in vitro and in vivo. The synergistic effect of cGAMP-mediated immunity and efficient anti-cancer effects successfully demonstrated the therapeutic potential of KAS-08 for combination therapy in cancer treatment.

scholarly journals Limonin: A Review of Its Pharmacology, Toxicity, and Pharmacokinetics

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3679 ◽  
Author(s):  
Fan ◽  
Zhang ◽  
Luo ◽  
Wang ◽  
Tang ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Pharmacological Activity ◽  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Metabolic Enzyme ◽  
Future Research ◽  
Pharmacokinetic Studies ◽  
Pharmacological Effects ◽  
Anti Cancer ◽  
Future Research Directions

Limonin is a natural tetracyclic triterpenoid compound, which widely exists in Euodia rutaecarpa (Juss.) Benth., Phellodendron chinense Schneid., and Coptis chinensis Franch. Its extensive pharmacological effects have attracted considerable attention in recent years. However, there is no systematic review focusing on the pharmacology, toxicity, and pharmacokinetics of limonin. Therefore, this review aimed to provide the latest information on the pharmacology, toxicity, and pharmacokinetics of limonin, exploring the therapeutic potential of this compound and looking for ways to improve efficacy and bioavailability. Limonin has a wide spectrum of pharmacological effects, including anti-cancer, anti-inflammatory and analgesic, anti-bacterial and anti-virus, anti-oxidation, liver protection properties. However, limonin has also been shown to lead to hepatotoxicity, renal toxicity, and genetic damage. Moreover, limonin also has complex impacts on hepatic metabolic enzyme. Pharmacokinetic studies have demonstrated that limonin has poor bioavailability, and the reduction, hydrolysis, and methylation are the main metabolic pathways of limonin. We also found that the position and group of the substituents of limonin are key in affecting pharmacological activity and bioavailability. However, some issues still exist, such as the mechanism of antioxidant activity of limonin not being clear. In addition, there are few studies on the toxicity mechanism of limonin, and the effects of limonin concentration on pharmacological effects and toxicity are not clear, and no researchers have reported any ways in which to reduce the toxicity of limonin. Therefore, future research directions include the mechanism of antioxidant activity of limonin, how the concentration of limonin affects pharmacological effects and toxicity, finding ways to reduce the toxicity of limonin, and structural modification of limonin—one of the key methods necessary to enhance pharmacological activity and bioavailability.

scholarly journals Evaluation of the anti-cancer potential of Cedrus deodara total lignans by inducing apoptosis of A549 cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaofeng Shi ◽  
Ruiqin Du ◽  
Junmin Zhang ◽  
Yanping Lei ◽  
Hongyun Guo
Keyword(s):  
Cell Cycle ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
A549 Cells ◽  
Cedrus Deodara ◽  
Anti Cancer ◽  
M Phase ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Lung Adenocarcinoma Cancer

Abstract Background Cedrus deodara (Roxb.) Loud (normally called as deodar), one out of four species in the genus Cedrus, exhibits widely biological activities. The Cedrus deodara total lignans from the pine needles (CTL) were extracted. The aim of the study was to investigate the anticancer potential of the CTL on A549 cell line. Methods We extracted the CTL by ethanol and assessed the cytotoxicity by CCK-8 method. Cell cycle and apoptosis were detected by a FACS Verse Calibur flow cytometry. Results The CTL were extracted by means of ethanol hot refluxing and the content of total lignans in CTL was about 55.77%. By the CCK-8 assays, CTL inhibited the growth of A549 cells in a dose-dependent fashion, with the IC50 values of 39.82 ± 1.74 μg/mL. CTL also inhibited the growth to a less extent in HeLa, HepG2, MKN28 and HT-29 cells. Conclusion At low doses, the CTL effectively inhibited the growth of A549 cells. By comparison of IC50 values, we found that A549 cells might be more sensitive to the treatment with CTL. In addition, CTL were also able to increase the population of A549 cells in G2/M phase and the percentage of apoptotic A549 cells. CTL may have therapeutic potential in lung adenocarcinoma cancer by regulating cell cycle and apoptosis.

Therapeutic potential of ceragenins and nanosystems containing membrane active compounds in the anti-cancer therapies

2019 ◽  
Vol 6 ◽  
pp. 21-32
Author(s):  
Ewelina Piktel ◽  
Robert Bucki
Keyword(s):  
Therapeutic Potential ◽  
Resistance Mechanism ◽  
Drug Carriers ◽  
Cancer Therapies ◽  
Mri Imaging ◽  
High Toxicity ◽  
Methods Development ◽  
Anti Cancer ◽  
Severity Of The Disease ◽  
Cancer Activity

Constantly increasing morbidity and mortality of cancer, complex immunopathogenesis of tumors and variable development and severity of the disease, enforce a constant search for new therapeutic factors with anti-cancer activity. Despite the constant achievements in anti- -cancer diagnostic and therapeutic methods development, the low specificity and high toxicity of cytostatics, and the multidrug resistance expansion, still remain a considerable health problem. Currently, natural, cationic antimicrobial peptides (AMPs) and their synthetic lipid analogs from the ceragenin group (CSA) are presented as potential antineoplastic compounds. Their special features, including the membrane permeabilizing-based mechanism of action, selectivity towards tumor cells, biocompatibility and the absence of a recorded anti-AMPs resistance mechanism, make cationic antineoplastic peptides an effective alternative to modern cytostatics. Moreover, a compelling number of research confirm the possibility of using magnetic nanoparticles as highly effective and biocompatible drug carriers, ensuring the achievement of a sufficiently high intracellular concentration of drug and thus, increasing its antineoplastic activity. The results obtained so far indicate the possibility of the employment of natural AMPs and their synthetic analogs from ceragenins group in an effective eradication of cancer cells. Nevertheless, further studies aiming to elucidate the safety of proposed nanosystems and focused on the employment of ceragenin-based nanosystems in diagnostic MRI imaging and as hyperthermia inducers are needed and justified.

scholarly journals Cancer-specific Therapeutic Potential of Resveratrol: Metabolic Approach against Hallmarks of Cancer

2013 ◽  
Vol 3 (8) ◽  
pp. 332 ◽  
Author(s):  
Dong Hoon Suh ◽  
Mi-Kyung Kim ◽  
Hee Seung Kim ◽  
Hyun Hoon Chung ◽  
Yong Sang Song
Keyword(s):  
Cancer Cells ◽  
Therapeutic Potential ◽  
Metabolic Reprogramming ◽  
Metabolic Demand ◽  
Macromolecular Synthesis ◽  
Invasion And Metastasis ◽  
Hallmarks Of Cancer ◽  
Cancer Hallmarks ◽  
Tissue Invasion ◽  
Anti Cancer

Cancer hallmarks include evading apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis. Cancer cells undergo metabolic reprogramming and inevitably take advantage of glycolysis to meet the increased metabolic demand: rapid energy generation and macromolecular synthesis. Resveratrol, a polyphenolic phytoalexin, is known to exhibit pleiotropic anti-cancer effects most of which are linked to metabolic reprogramming in cancer cells. This review summarizes various anti-cancer effects of resveratrol in the context of cancer hallmarks in relation to metabolic reprogramming.

Sign in / Sign up

Export Citation Format

Share Document