morin and Neoplasms

Flavonoids represent polyphenolic plant secondary metabolites with a general structure of a 15-carbon skeleton comprising two phenyl rings and a heterocyclic ring. Over 5000 natural flavonoids (flavanones, flavanonols, and flavans) from various plants have been characterized. Several studies provide novel and promising insights into morin hydrate for its different biological activities against a series of metabolic syndromes. The present review is a rendition of its sources, chemistry, functional potency, and protective effects on metabolic syndromes ranging from cancer to brain injury. Most importantly this systematic review article also highlights the mechanisms of interest to morin-mediated management of metabolic disorders. The key mechanisms (anti-oxidative and anti-inflammatory) responsible for its therapeutic potential are well featured after collating the in vitro and in vivo study reports. As a whole, based on the prevailing information rationalizing its medicinal use, morin can be identified as a therapeutic agent for the expansion of human health.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Flavonoids; Food Ingredients; Functional Food; Humans; Metabolic Diseases; Neoplasms

Protein kinases have been important targets for antitumor targets due to their key roles in regulating multiple cell signaling pathways. Numerous compounds containing flavonoid scaffold as an indispensable anchor have been found to be potent inhibitors of protein kinases. Some of these flavonoids have been in clinical research as protein kinases inhibitors. Thus, the present review mainly focuses on the structural requirement for anticancer potential of flavone derivatives targeting several key serine/threonine protein kinases. This information may provide an opportunity to scientists of medicinal chemistry to design multi-functional flavone derivatives for the treatment of cancer.

Topics: Animals; Antineoplastic Agents; Flavones; Humans; Neoplasms; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases

The emergence of drug resistance, coupled with the issue of low tumor selectivity and toxicity is a major pitfall in cancer chemotherapy. It has necessitated the urgent need for the discovery of less toxic and more potent new anti-cancer pharmaceuticals, which target the interactive mechanisms involved in division and metastasis of cancer cells. Human DNA ligase I (hligI) plays an important role in DNA replication by linking Okazaki fragments on the lagging strand of DNA, and also participates in DNA damage repair processes. Dysregulation of the functioning of such ligases can severely impact DNA replication and repair pathways events that are generally targeted in cancer treatment. Although, several human DNA ligase inhibitors have been reported in the literature but unfortunately not a single inhibitor is currently being used in cancer chemotherapy. Results of pre-clinical studies also support the fact that human DNA ligases are an attractive target for the development of new anticancer agents which work by the selective inhibition of rapidly proliferating cancer cells. In this manuscript, we discuss, in brief, the structure, synthesis, structure-activity-relationship (SAR) and anticancer activity of recently reported hLigI inhibitors.

Topics: Antineoplastic Agents; Cell Proliferation; DNA Ligase ATP; Enzyme Inhibitors; Humans; Neoplasms; Structure-Activity Relationship

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

AKR1B10 is an NADPH-dependent reductase that plays an important function in several physiological reactions such as the conversion of retinal to retinol, reduction of isoprenyl aldehydes, and biotransformation of procarcinogens and drugs. A growing body of evidence points to the important role of the enzyme in the development of several types of cancer (e.g., breast, hepatocellular), in which it is highly overexpressed. AKR1B10 is regarded as a therapeutic target for the treatment of these diseases, and potent and specific inhibitors may be promising therapeutic agents. Several inhibitors of AKR1B10 have been described, but the area of natural plant products has been investigated sparingly. In the present study almost 40 diverse phenolic compounds and alkaloids were examined for their ability to inhibit the recombinant AKR1B10 enzyme. The most potent inhibitors-apigenin, luteolin, and 7-hydroxyflavone-were further characterized in terms of IC50, selectivity, and mode of action. Molecular docking studies were also conducted, which identified putative binding residues important for the interaction. In addition, cellular studies demonstrated a significant inhibition of the AKR1B10-mediated reduction of daunorubicin in intact cells by these inhibitors without a considerable cytotoxic effect. Although these compounds are moderately potent and selective inhibitors of AKR1B10, they constitute a new structural type of AKR1B10 inhibitor and may serve as a template for the development of better inhibitors.

Topics: Aldehyde Reductase; Aldo-Keto Reductases; Apigenin; Daunorubicin; Enzyme Inhibitors; Flavones; Flavonoids; HCT116 Cells; Humans; Luteolin; Molecular Conformation; Molecular Structure; Neoplasms

Topics: Animals; Antineoplastic Agents; Antitubercular Agents; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Resistance; Isoenzymes; Models, Molecular; Molecular Targeted Therapy; Mycobacterium tuberculosis; Neoplasms; Protein Conformation; Protein Tyrosine Phosphatases; Proto-Oncogene Proteins

Topics: Acetyl-CoA Carboxylase; Animals; Antineoplastic Agents; ATP Citrate (pro-S)-Lyase; Biosynthetic Pathways; Fatty Acid Synthases; Fatty Acids; Humans; Lipogenesis; Models, Chemical; Molecular Structure; Neoplasms

The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded new insight into brain cancer. However, the complete repertoire of signaling pathways that governs the proliferation and self-renewal of NSCs, which we refer to as the 'ground state', remains largely uncharacterized. Although the candidate gene approach has uncovered vital pathways in NSC biology, so far only a few highly studied pathways have been investigated. Based on the intimate relationship between NSC self-renewal and neurosphere proliferation, we undertook a chemical genetic screen for inhibitors of neurosphere proliferation in order to probe the operational circuitry of the NSC. The screen recovered small molecules known to affect neurotransmission pathways previously thought to operate primarily in the mature central nervous system; these compounds also had potent inhibitory effects on cultures enriched for brain cancer stem cells. These results suggest that clinically approved neuromodulators may remodel the mature central nervous system and find application in the treatment of brain cancer.

Topics: Animals; Cell Survival; Cells, Cultured; Mice; Molecular Structure; Neoplasms; Neurons; Pharmaceutical Preparations; Sensitivity and Specificity; Stem Cells