scholarly journals Flavonoids: Molecular Mechanism Behind Natural Chemoprotective Behavior-A Mini Review

2021 ◽  
Vol 12 (5) ◽  
pp. 5983-5995
Keyword(s):  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Apoptosis Induction ◽  
Antioxidative Effect ◽  
Pharmacological Activities ◽  
Activity Inhibition ◽  
Metabolic Action ◽  
The Given

The given review summarizes the various molecular mechanisms responsible for the metabolic action of flavonoids as anticancer agents. Various types of flavonoids have proven to show biological & pharmacological activities like anti-inflammatory, antimicrobial, antioxidant, anticancer, anti-allergic, and antidiarrheal activities. The chemoprotective nature of flavonoids is also discussed due to their ability to inhibit topoisomerase enzymes at various stages of cancer, such as tumor initiation, promotion, and progression. The various biomolecular activities which are responsible for their role as the chemopreventive agent may be due to their antioxidative effect, anti-angiogenic properties, induction of protective enzymes, inhibitory action on the cell-like protein kinase activity inhibition, spreading of tumor cells, apoptosis induction, tumor cell invasion to name a few. There has been much-emerging evidence based on the versatility of flavonoids, their complex mechanism of action, lesser side effects, and varied pharmacological properties that make them potential anticancer agents. Challenges associated with their use in extraction, isolation, purification, and checking bioefficacy are also discussed.

scholarly journals Protein kinase activity of the insulin receptor

1986 ◽  
Vol 235 (1) ◽  
pp. 1-11 ◽  
Author(s):  
S Gammeltoft ◽  
E Van Obberghen
Keyword(s):  
Insulin Receptor ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Beta Subunit ◽  
Alpha Subunit ◽  
Beta Subunits ◽  
Protein Kinase Activity ◽  
Intact Cells ◽  
Receptor Complexes ◽  
Alpha Subunits

The insulin receptor is an integral membrane glycoprotein (Mr approximately 300,000) composed of two alpha-subunits (Mr approximately 130,000) and two beta-subunits (Mr approximately 95,000) linked by disulphide bonds. This oligomeric structure divides the receptor into two functional domains such that alpha-subunits bind insulin and beta-subunits possess tyrosine kinase activity. The amino acid sequence deduced from cDNA of the single polypeptide chain precursor of human placental insulin receptor revealed that alpha- and beta-subunits consist of 735 and 620 residues, respectively. The alpha-subunit is hydrophilic, disulphide-bonded, glycosylated and probably extracellular. The beta-subunit consists of a short extracellular region which links the alpha-subunit through disulphide bridges, a hydrophobic transmembrane region and a longer cytoplasmic region which is structurally homologous with other tyrosine kinases like the src oncogene product and EGF receptor kinases. The cellular function of insulin receptors is dual: transmembrane signalling and endocytosis of hormone. The binding of insulin to its receptor on the cell membrane induces transfer of signal from extracellular to cytoplasmic receptor domains leading to activation of cell metabolism and growth. In addition, hormone-receptor complexes are internalized leading to intracellular proteolysis of insulin, whereas receptors are recycled to the membrane. These phenomena are kinetically well-characterized, but their molecular mechanisms remain obscure. Insulin receptor in different tissues and animal species are homologous in their structure and function, but show also significant differences regarding size of alpha-subunits, binding kinetics, insulin specificity and receptor-mediated degradation. We suggest that this heterogeneity of receptors may be linked to the diversity in insulin effects on metabolism and growth in various cell types. The purified insulin receptor phosphorylates its own beta-subunit and exogenous protein and peptide substrates on tyrosine residues, a reaction which is insulin-sensitive, Mn2+-dependent and specific for ATP. Tyrosine phosphorylation of the beta-subunit activates receptor kinase activity, and dephosphorylation with alkaline phosphatase deactivates the kinase. In intact cells or impure receptor preparations, a serine kinase is also activated by insulin. The cellular role of two kinase activities associated with the insulin receptor is not known, but we propose that the tyrosine- and serine-specific kinases mediate insulin actions on metabolism and growth either through dual-signalling or sequential pathways.(ABSTRACT TRUNCATED AT 400 WORDS)

Soluble polycations and cationic amphiphiles inhibit volume-sensitive K-Cl cotransport in human red cell ghosts

1994 ◽  
Vol 266 (4) ◽  
pp. C997-C1005 ◽  
Author(s):  
J. R. Sachs
Keyword(s):  
Kinase Activity ◽  
Membrane Surface ◽  
Protein Kinase Activity ◽  
Red Cell ◽  
Effective Inhibitor ◽  
Inner Membrane ◽  
Cationic Amphiphiles ◽  
Activity Inhibition ◽  
High K ◽  
K Concentration

We have measured the effect of soluble polycations (spermine and methylglyoxal) and cationic amphiphiles (sphingosine and tetracaine) on K-Cl cotransport in shrunken and swollen red cell ghosts. All substances inhibited cotransport, and for each agent, the concentration at which inhibition was half-maximal was about the same for swollen and shrunken ghosts. Acetylspermine was a much less effective inhibitor than spermine, which demonstrates that inhibition depends on the cationic groups of spermine. Spermine was a more effective inhibitor in ATP-free ghosts than in ghosts containing ATP, which eliminates the possibility that inhibition of cotransport activity results from inhibition of protein kinase activity. Inhibition by spermine is as effective in K-free ghosts as in high-K ghosts; spermine does not inhibit cotransport by reducing the effective K concentration at the inner membrane surface. We conclude that regulation of K-Cl cotransport involves negative charges (phosphatidylserine or phosphatidylinositides) at the inner membrane surface and suggest a model that accounts for our findings.

Heme: emergent roles of heme in signal transduction, functional regulation and as catalytic centres

2019 ◽  
Vol 48 (24) ◽  
pp. 5624-5657 ◽  
Author(s):  
Toru Shimizu ◽  
Alzbeta Lengalova ◽  
Václav Martínek ◽  
Markéta Martínková
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Dna Binding ◽  
Heme Proteins ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Bond Formation ◽  
Dna Binding Protein ◽  
Protein Kinase Activity ◽  
Functional Regulation

Molecular mechanisms of unprecedented functions of exchangeable/labile heme and heme proteins including transcription, DNA binding, protein kinase activity, K+ channel functions, cis–trans isomerization, N–N bond formation, and other functions are described.

scholarly journals Antiproliferative Effect of Chloroform Extract of Cangkring Leaves (Erythrina fusca Lour.) and Its Isolates against HeLa Cells

2012 ◽  
Vol 3 (1) ◽  
pp. 358
Author(s):  
Endah Puspitasari ◽  
Endah Dwi Setyowati ◽  
Binar Asrining Dhiani ◽  
Sugeng Riyanto
Keyword(s):  
Cervical Cancer ◽  
Hela Cells ◽  
Doubling Time ◽  
Molecular Mechanisms ◽  
Chloroform Extract ◽  
Apoptosis Induction ◽  
Counting Method ◽  
Cervical Cancer Cells ◽  
Direct Counting ◽  
The Given

Cervical cancer is a type of cancer possessing the 3rd highest incidence among women worldwide. Today’s therapies against cancer are still ineffective, thus people are seeking for alternative method. Erythrina fusca Lour. has been used traditionally as anticancer. This experiment is conducted to study the ability of chloroform extract of E. fusca Lour. leaves and its isolates on HeLa cervical cancer cells. The cytotoxicity assay and doubling time assay were done using direct counting method, while the DNA staining assay was done using acrydine orange. The chloroform extract and isolate # 30 showed cytotoxic activity with IC50 of 16 and 5 µg/ml, respectively, while isolate # 2 and isolate # 8 didn’t. The effluent # 30 could not affect HeLa cells growth at the given concentration, but it might promote DNA fragmentation indicating apoptosis induction. The molecular mechanisms underlying these effects still need to be further explored.Keywords: Erythrina fusca Lour., isolate and effluent of chloroform extract, antiproliferative, cervical cancer

Effect of Thrombin on Phosphorylation of Platelet Membrane Proteins

1976 ◽  
Vol 35 (03) ◽  
pp. 635-642 ◽  
Author(s):  
M Steiner
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Qualitative Change ◽  
Protein Kinase Activity ◽  
Protein Substrates ◽  
Phosphoprotein Phosphatase ◽  
Progressive Loss ◽  
Platelet Membranes ◽  
Endogenous Protein ◽  
Considerable Loss

SummaryThe effect of thrombin on the phosphorylating activity of platelet membranes was compared to that of trypsin. Preincubation of non-32P phosphorylated platelet membranes with or without either of these two enzymes resulted in a considerable loss of membrane protein kinase activity which was most severe when trypsin was used. Protein kinase activity and endogenous protein acceptors decreased in parallel. 32P-phosphorylated membranes showed a slow but progressive loss of label which was accelerated by trypsin. Thrombin under these conditions prevented the loss of 32P-phosphate. These results are interpreted to indicate a thrombin-induced destruction of a phosphoprotein phosphatase. The protein kinase activity of phosphorylated platelet membranes using endogenous or exogenous protein substrates showed a significant reduction compared to non-phosphorylated membranes suggesting a deactivation of protein kinase by phosphorylation of platelet membranes. Neither thrombin nor trypsin caused a qualitative change in the membrane polypeptides accepting 32P-phosphate but resulted in quantitative alterations of their ability to become phosphorylated.

Anticancer Activity of Natural Flavonoids: Inhibition of HIF-1α Signaling Pathway

2020 ◽  
Vol 23 (26) ◽  
pp. 2945-2959 ◽  
Author(s):  
Xiangping Deng ◽  
Yijiao Peng ◽  
Jingduo Zhao ◽  
Xiaoyong Lei ◽  
Xing Zheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Pharmacological Activities ◽  
Hypoxia Inducible Factor 1 ◽  
The Past ◽  
Low Toxicity ◽  
Tumor Blood Vessels

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.

Anticancer Agents Based on Vulnerable Components in a Signalling Pathway

2020 ◽  
Vol 20 (10) ◽  
pp. 886-907 ◽  
Author(s):  
Ankur Vaidya ◽  
Shweta Jain ◽  
Sanjeev Sahu ◽  
Pankaj Kumar Jain ◽  
Kamla Pathak ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Dna Methyltransferase ◽  
Leucine Zipper ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
Sphingosine Kinase 2 ◽  
Family Protein ◽  
Rational Combination ◽  
Protein Kinase Akt ◽  
Parp 1

Traditional cancer treatment includes surgery, chemotherapy, radiotherapy and immunotherapy that are clinically beneficial, but are associated with drawbacks such as drug resistance and side effects. In quest for better treatment, many new molecular targets have been introduced in the last few decades. Finding new molecular mechanisms encourages researchers to discover new anticancer agents. Exploring the mechanism of action also facilitates anticipation of potential resistance mechanisms and optimization of rational combination therapies. The write up describes the leading molecular mechanisms for cancer therapy, including mTOR, tyrosine Wee1 kinase (WEE1), Janus kinases, PI3K/mTOR signaling pathway, serine/threonine protein kinase AKT, checkpoint kinase 1 (Chk1), maternal embryonic leucine-zipper kinase (MELK), DNA methyltransferase I (DNMT1), poly (ADP-ribose) polymerase (PARP)-1/-2, sphingosine kinase-2 (SK2), pan-FGFR, inhibitor of apoptosis (IAP), murine double minute 2 (MDM2), Bcl-2 family protein and reactive oxygen species 1 (ROS1). Additionally, the manuscript reviews the anticancer drugs currently under clinical trials.

Natural Products for Regulating Macrophages M2 Polarization

2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Research Progress ◽  
Cellular Mechanisms ◽  
Pharmacological Activities ◽  
Current Review ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
Herbal Plants

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

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