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1.
A Review on Sources and Pharmacological Aspects of Sakuranetin.
Stompor, M
Nutrients. 2020;(2)
Abstract
Sakuranetin belongs to the group of methoxylated flavanones. It is widely distributed in Polyomnia fruticosa and rice, where it acts as a phytoalexin. Other natural sources of this compound are, among others, grass trees, shrubs, flowering plants, cheery, and some herbal drugs, where it has been found in the form of glycosides (mainly sakuranin). Sakuranetin has antiproliferative activity against human cell lines typical for B16BL6 melanoma, esophageal squamous cell carcinoma (ESCC) and colon cancer (Colo 320). Moreover, sakuranetin shows antiviral activity towards human rhinovirus 3 and influenza B virus and was reported to have antioxidant, antimicrobial, antiinflammatory, antiparasitic, antimutagenic, and antiallergic properties. The aim of this review is to present the current status of knowledge of pro-health properties of sakuranetin.
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2.
Recent Advances in the Development of "Curcumin Inspired" Compounds as New Therapeutic Agents.
Borosky, GL, Laali, KK
Mini reviews in medicinal chemistry. 2020;(15):1543-1558
Abstract
Despite a huge body of research in the past two decades investigating the antioxidant, antiinflammatory, anti-microbial, and anti-carcinogenic properties of curcumin (CUR), a CUR-based antitumor drug is yet to be developed. Lack of success in achieving this goal stems from CUR's unfavorable biophysicochemical features, particularly poor solubility, low bioavailability, and rapid metabolism, coupled with a complex biological profile making it difficult to determine its mechanism of action. A significant body of literature aimed at improving its physicochemical properties through synthesis or by designing delivery methods has been published, and the progress in these areas has been reviewed. The present review aims to summarize recent progress in the synthesis of structurally diverse "curcumin-inspired" compounds along with computational docking and bioassay studies, through which a number of promising analogs have been identified that warrant further study.
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3.
Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel.
Naz, I, Ramchandani, S, Khan, MR, Yang, MH, Ahn, KS
Molecules (Basel, Switzerland). 2020;(5)
Abstract
Natural compounds extracted from plants have gained immense importance in the fight against cancer cells due to their lesser toxicity and potential therapeutic effects. Raddeanin A (RA), an oleanane type triterpenoid is a major compound isolated from Anemone raddeana Regel. As an anticancer agent, RA induces apoptosis, cell cycle arrest, inhibits invasion, migration and angiogenesis in malignant cell lines as well as in preclinical models. In this systemic review, the pharmacological effects of RA and its underlying molecular mechanisms were carefully analyzed and potential molecular targets have been highlighted. The apoptotic potential of RA can be mediated through the modulation of Bcl-2, Bax, caspase-3, caspase-8, caspase-9, cytochrome c and poly-ADP ribose polymerase (PARP) cleavage. PI3K/Akt signaling pathway serves as the major molecular target affected by RA. Furthermore, RA can block cell proliferation through inhibition of canonical Wnt/β-catenin signaling pathway in colorectal cancer cells. RA can also alter the activation of NF-κB and STAT3 signaling pathways to suppress invasion and metastasis. RA has also exhibited promising anticancer potential against drug resistant cancer cells and can enhance the anticancer effects of several chemotherapeutic agents. Overall, RA may function as a promising compound in combating cancer, although further in-depth study is required under clinical settings to validate its efficacy in cancer patients.
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4.
Genistein: Its Role in Breast Cancer Growth and Metastasis.
Mukund, V
Current drug metabolism. 2020;(1):6-10
Abstract
BACKGROUND Genistein being a phytoestrogen imitates the characteristics of estrogen, which can be useful to treat conditions by reducing the estrogen levels at the time of menopause, osteoporosis and high risk for breast cancer. OBJECTIVE The superior binding of genistein to ERβ might help in reducing breast malignancy risk. CONCLUSION Genistein induces cell cycle arrest, anti-metastatic properties and ultimately affects the breast cancer cell growth by multiple mechanisms. Genistein-mediated anti-proliferative or anti-growth effects are usually observed at higher concentrations. These signaling pathways involve the decrease of NF-κB, HIF-1α, VEGF, and an increase of tumor suppressor p21. This will provide further insight into understanding the biology of transcription factors NF-κB, and HIF-1α in breast cancer.
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5.
The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase.
Manley, PW, Barys, L, Cowan-Jacob, SW
Leukemia research. 2020;:106458
Abstract
Asciminib is a potent, orally bioavailable, investigational drug that specifically and potently inhibits the tyrosine kinase activity of native ABL1, together with that of the chimeric BCR-ABL1 oncoprotein which causes chronic myeloid leukemia (CML). In contrast to ATP-competitive BCR-ABL1 kinase inhibitors employed to treat CML that target multiple kinases, asciminib binds to the myristate binding pocket on the kinase domains of ABL1 and BCR-ABL1. Hitherto no drugs have been developed whose mechanism of action involves interacting with myristate binding pockets on proteins, and analysis of the structures of such binding sites in proteins other than ABL1/ABL2/BCR-ABL1 strongly suggest that asciminib will not bind to these with high affinity. Accordingly, the drug has no known safety liabilities resulting from any off-target activity, as illustrated by its specificity towards cells expressing BCR-ABL1 and lack of effects on non-kinase targets in biochemical screens. Because asciminib does not bind to the ATP-binding site it maintains substantial activity against kinase domain mutations that impart acquired drug resistance to ATP-competitive drugs. However, in vitro studies in cells have identified BCR-ABL1 mutations that reduce the anti-proliferative activity of asciminib, some of which are associated with clinical resistance towards the drug in patients. Here we review effects of asciminib on mutant forms of BCR-ABL1, analyse their sensitivity towards the drug from a structural perspective and affirm support for employing combinations with ATP-competitive inhibitors to impede the reactivation of BCR-ABL1 kinase activity in patients receiving monotherapy.
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6.
Chemical probes for protein arginine methyltransferases.
Li, ASM, Li, F, Eram, MS, Bolotokova, A, Dela Seña, CC, Vedadi, M
Methods (San Diego, Calif.). 2020;:30-43
Abstract
Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups to specific arginine residues of their substrates using S-adenosylmethionine as a methyl donor, contributing to regulation of many biological processes including transcription, and DNA damage repair. Dysregulation of PRMT expression is often associated with various diseases including cancers. Different methods have been used to characterize the activities of PRMTs and determine their kinetic parameters including mass spectrometry, radiometric, and antibody-based assays. Here, we present kinetic characterization of PRMTs using a radioactivity-based assay for better comparison along with previously reported values. We also report on full characterization of PRMT9 activity with SAP145 peptide as substrate. We further review the potent, selective and cell-active PRMT inhibitors discovered in recent years to provide a better understanding of available tools to investigate the roles these proteins play in health and disease.
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7.
Annexin A1 involved in the regulation of inflammation and cell signaling pathways.
Han, PF, Che, XD, Li, HZ, Gao, YY, Wei, XC, Li, PC
Chinese journal of traumatology = Zhonghua chuang shang za zhi. 2020;(2):96-101
Abstract
With the deepening of research, proteomics has developed into a science covering the study of all the structural and functional characteristics of proteins and the dynamic change rules. The essence of various biological activities is revealed from the perspectives of the biological structure, functional activity and corresponding regulatory mechanism of proteins by proteomics. Among them, phospholipid-binding protein is one of the hotspots of proteomics, especially annexin A1, which is widely present in various tissues and cells of the body. It has the capability of binding to phospholipid membranes reversibly in a calcium ion dependent manner. In order to provide possible research ideas for researchers, who are interested in this protein, the biological effects of annexin A1, such as inflammatory regulation, cell signal transduction, cell proliferation, differentiation and apoptosis are described in this paper.
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8.
New aspects of amino acid metabolism in cancer.
Vettore, L, Westbrook, RL, Tennant, DA
British journal of cancer. 2020;(2):150-156
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Abstract
An abundant supply of amino acids is important for cancers to sustain their proliferative drive. Alongside their direct role as substrates for protein synthesis, they can have roles in energy generation, driving the synthesis of nucleosides and maintenance of cellular redox homoeostasis. As cancer cells exist within a complex and often nutrient-poor microenvironment, they sometimes exist as part of a metabolic community, forming relationships that can be both symbiotic and parasitic. Indeed, this is particularly evident in cancers that are auxotrophic for particular amino acids. This review discusses the stromal/cancer cell relationship, by using examples to illustrate a number of different ways in which cancer cells can rely on and contribute to their microenvironment - both as a stable network and in response to therapy. In addition, it examines situations when amino acid synthesis is driven through metabolic coupling to other reactions, and synthesis is in excess of the cancer cell's proliferative demand. Finally, it highlights the understudied area of non-proteinogenic amino acids in cancer metabolism and their potential role.
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9.
An Overview of the Potential Antineoplastic Effects of Casticin.
Ramchandani, S, Naz, I, Lee, JH, Khan, MR, Ahn, KS
Molecules (Basel, Switzerland). 2020;(6)
Abstract
Cancer persists as one of the leading causes of deaths worldwide, contributing to approximately 9.6 million deaths per annum in recent years. Despite the numerous advancements in cancer treatment, there is still abundant scope to mitigate recurrence, adverse side effects and toxicities caused by existing pharmaceutical drugs. To achieve this, many phytochemicals from plants and natural products have been tested against cancer cell lines in vivo and in vitro. Likewise, casticin, a flavonoid extracted from the Vitex species, has been isolated from the leaves and seeds of V. trifolia and V. agnus-castus. Casticin possesses a wide range of therapeutic properties, including analgesic, anti-inflammatory, antiangiogenic, antiasthmatic and antineoplastic activities. Several studies have been conducted on the anticancer effects of casticin against cancers, including breast, bladder, oral, lung, leukemia and hepatocellular carcinomas. The compound inhibits invasion, migration and proliferation and induces apoptosis (casticin-induced, ROS-mediated and mitochondrial-dependent) and cell cycle arrest (G0/G1, G2/M, etc.) through different signaling pathways, namely the PI3K/Akt, NF-κB, STAT3 and FOXO3a/FoxM1 pathways. This review summarizes the chemo-preventive ability of casticin as an antineoplastic agent against several malignancies.
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10.
The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects.
Ryskalin, L, Biagioni, F, Busceti, CL, Lazzeri, G, Frati, A, Fornai, F
Molecules (Basel, Switzerland). 2020;(20)
Abstract
The present review focuses on the multi-faceted effects of curcumin on the neurobiology glioblastoma multiforme (GBM), with a special emphasis on autophagy (ATG)-dependent molecular pathways activated by such a natural polyphenol. This is consistent with the effects of curcumin in a variety of experimental models of neurodegeneration, where the molecular events partially overlap with GBM. In fact, curcumin broadly affects various signaling pathways, which are similarly affected in cell degeneration and cell differentiation. The antitumoral effects of curcumin include growth inhibition, cell cycle arrest, anti-migration and anti-invasion, as well as chemo- and radio-sensitizing activity. Remarkably, most of these effects rely on mammalian target of rapamycin (mTOR)-dependent ATG induction. In addition, curcumin targets undifferentiated and highly tumorigenic GBM cancer stem cells (GSCs). When rescuing ATG with curcumin, the tumorigenic feature of GSCs is suppressed, thus counteracting GBM establishment and growth. It is noteworthy that targeting GSCs may also help overcome therapeutic resistance and reduce tumor relapse, which may lead to a significant improvement of GBM prognosis. The present review focuses on the multi-faceted effects of curcumin on GBM neurobiology, which represents an extension to its neuroprotective efficacy.