scholarly journals A REVIEW ON BIOACTIVE PHYTOCHEMICALS AND IT’S MECHANISM ON CANCER TREATMENT AND PREVENTION BY TARGETING MULTIPLE CELLULAR SIGNALING PATHWAYS

2021 ◽  
pp. 15-19
Author(s):  
VARSHA L. BHUTADIYA ◽  
KINNARI N. MISTRY
Keyword(s):  
Curcuma Longa ◽  
Developed Countries ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Therapies ◽  
Anticancer Activities ◽  
Treatment And Prevention ◽  
Mitogen Activated Protein ◽  
Beneficial Impact ◽  
Impact On Survival

In developing and developed countries, cancer is a significant health problem in people. Cancer becomes the second greatest cause of death in human after cardiovascular disease. However, significant advancements in modern cancer therapies have a beneficial impact on survival, chemotherapy and radiation therapy. Plants fulfill our basic needs to continue life and provide natural products that help to cure disease. The medicinal plants are readily available and have no toxicity as compared to modern drugs. Phytochemicals act on metabolic pathways and inhibit tumor growth, the development of cancerous cells, and replication by different mechanisms. Apigenin's chemo-preventive and anticancer activities have been demonstrating in numerous studies. Curcumin is a polyphenolic compound isolated from the Curcuma longa plant. EGCG, a polyphenol in black, white, and green tea is a chemo-preventive effect against many cancers by targeting multiple pathways. Normal cell growth and cell proliferation are closely regulated processes. The JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway controls gene expression during different processes, including proliferation, initiation, and apoptosis. The transcription factors are associated with the growth of cancer cells and control a cellular function in the disease. Mitogen-activated protein kinase (MAPK) is a class of serine and threonine kinase that includes ERK (extracellular regulated kinase), JNK (c-Jun N-terminal kinases), and p38. This review paper describes natural phytochemical compounds, their molecular targets and mechanisms of action.

scholarly journals Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4511-4522 ◽  
Author(s):  
Florian Grebien ◽  
Marc A. Kerenyi ◽  
Boris Kovacic ◽  
Thomas Kolbe ◽  
Verena Becker ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Independent Manner ◽  
Hematopoietic Stem ◽  
Tyrosine Kinase Signaling ◽  
Fusion Construct ◽  
Downstream Effector ◽  
Kit Receptor ◽  
Mitogen Activated Protein

Abstract Erythropoiesis requires erythropoietin (Epo) and stem cell factor (SCF) signaling via their receptors EpoR and c-Kit. EpoR, like many other receptors involved in hematopoiesis, acts via the kinase Jak2. Deletion of EpoR or Janus kinase 2 (Jak2) causes embryonic lethality as a result of defective erythropoiesis. The contribution of distinct EpoR/Jak2-induced signaling pathways (mitogen-activated protein kinase, phosphatidylinositol 3-kinase, signal transducer and activator of transcription 5 [Stat5]) to functional erythropoiesis is incompletely understood. Here we demonstrate that expression of a constitutively activated Stat5a mutant (cS5) was sufficient to relieve the proliferation defect of Jak2−/− and EpoR−/− cells in an Epo-independent manner. In addition, tamoxifen-induced DNA binding of a Stat5a–estrogen receptor (ER)* fusion construct enabled erythropoiesis in the absence of Epo. Furthermore, c-Kit was able to enhance signaling through the Jak2-Stat5 axis, particularly in lymphoid and myeloid progenitors. Although abundance of hematopoietic stem cells was 2.5-fold reduced in Jak2−/− fetal livers, transplantation of Jak2−/−-cS5 fetal liver cells into irradiated mice gave rise to mature erythroid and myeloid cells of donor origin up to 6 months after transplantation. Cytokine- and c-Kit pathways do not function independently of each other in hematopoiesis but cooperate to attain full Jak2/Stat5 activation. In conclusion, activated Stat5 is a critical downstream effector of Jak2 in erythropoiesis/myelopoiesis, and Jak2 functionally links cytokine- with c-Kit-receptor tyrosine kinase signaling.

scholarly journals Playing the Whack-A-Mole Game: ERK5 Activation Emerges Among the Resistance Mechanisms to RAF-MEK1/2-ERK1/2- Targeted Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Alessandro Tubita ◽  
Ignazia Tusa ◽  
Elisabetta Rovida
Keyword(s):  
Tyrosine Kinases ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Therapies ◽  
New Era ◽  
Mitogen Activated Protein ◽  
The Impact ◽  
The Ideal

Molecularly tailored therapies have opened a new era, chronic myeloid leukemia being the ideal example, in the treatment of cancer. However, available therapeutic options are still unsatisfactory in many types of cancer, and often fail due to the occurrence of resistance mechanisms. With regard to small-molecule compounds targeting the components of the Mitogen-Activated Protein Kinase (MAPK) cascade RAF-MEK1/2-ERK1/2, these drugs may result ineffective as a consequence of the activation of compensatory pro-survival/proliferative signals, including receptor tyrosine kinases, PI3K, as well as other components of the MAPK family such as TPL2/COT. The MAPK ERK5 has been identified as a key signaling molecule in the biology of several types of cancer. In this review, we report pieces of evidence regarding the activation of the MEK5-ERK5 pathway as a resistance mechanism to RAF-MEK1/2-ERK1/2 inhibitors. We also highlight the known and possible mechanisms underlying the cross-talks between the ERK1/2 and the ERK5 pathways, the characterization of which is of great importance to maximize, in the future, the impact of RAF-MEK1/2-ERK1/2 targeting. Finally, we emphasize the need of developing additional therapeutically relevant MEK5-ERK5 inhibitors to be used for combined treatments, thus preventing the onset of resistance to cancer therapies relying on RAF-MEK1/2-ERK1/2 inhibitors.

scholarly journals Molecular Targets of Genistein and Its Related Flavonoids to Exert Anticancer Effects

2019 ◽  
Vol 20 (10) ◽  
pp. 2420 ◽  
Author(s):  
Hee-Sung Chae ◽  
Rong Xu ◽  
Jae-Yeon Won ◽  
Young-Won Chin ◽  
Hyungshin Yim
Keyword(s):  
Biological Effects ◽  
Survival Rates ◽  
Mitogen Activated Protein Kinase ◽  
Anticancer Activities ◽  
Biological Targets ◽  
Cycle Arrest ◽  
Specific Effects ◽  
Anticancer Effects ◽  
Mitogen Activated Protein ◽  
Phosphoinositide 3 Kinase

Increased health awareness among the public has highlighted the health benefits of dietary supplements including flavonoids. As flavonoids target several critical factors to exert a variety of biological effects, studies to identify their target-specific effects have been conducted. Herein, we discuss the basic structures of flavonoids and their anticancer activities in relation to the specific biological targets acted upon by these flavonoids. Flavonoids target several signaling pathways involved in apoptosis, cell cycle arrest, mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/AKT kinase, and metastasis. Polo-like kinase 1 (PLK1) has been recognized as a valuable target in cancer treatment due to the prognostic implication of PLK1 in cancer patients and its clinical relevance between the overexpression of PLK1 and the reduced survival rates of several carcinoma patients. Recent studies suggest that several flavonoids, including genistein directly inhibit PLK1 inhibitory activity. Later, we focus on the anticancer effects of genistein through inhibition of PLK1.

Interleukin-6 and interleukin-11: same same but different

2013 ◽  
Vol 394 (9) ◽  
pp. 1145-1161 ◽  
Author(s):  
Christoph Garbers ◽  
Jürgen Scheller
Keyword(s):  
Neuronal Development ◽  
Inflammatory Diseases ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Cytokine Signaling ◽  
Downstream Signaling ◽  
Mitogen Activated Protein ◽  
Β Receptor ◽  
Redundant Functions

Abstract The pleiotropic physiological functions of interleukin (IL-)6 type cytokines range from embryonic development and tissue homoeostasis to neuronal development and T cell differentiation. In contrast, imbalance of the well-controlled cytokine signaling network leads to chronic inflammatory diseases and cancer. IL-6 and IL-11 both signal through a homodimer of the ubiquitously expressed β-receptor glycoprotein 130 (gp130). Specificity is gained through an individual IL-6/IL-11 α-receptor, which does not directly participate in signal transduction, although the initial cytokine binding event to the α-receptor leads to the final complex formation with the β-receptors. Both cytokines activate the same downstream signaling pathways, which are predominantly the mitogen-activated protein kinase (MAPK)-cascade and the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway. However, recent studies have highlighted divergent roles of the two related cytokines. Here, we will discuss how the biochemical similarities are translated into unique and non-redundant functions of IL-6 and IL-11 in vivo and illustrate strategies for cytokine-specific therapeutic intervention.

scholarly journals Emerging EPO and EPO receptor regulators and signal transducers

Blood ◽  
2015 ◽  
Vol 125 (23) ◽  
pp. 3536-3541 ◽  
Author(s):  
David Kuhrt ◽  
Don M. Wojchowski
Keyword(s):  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Cell Surface Receptor ◽  
Erythroid Progenitors ◽  
Epo Receptor ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Surface Receptor

Abstract As essential mediators of red cell production, erythropoietin (EPO) and its cell surface receptor (EPO receptor [EPOR]) have been intensely studied. Early investigations defined basic mechanisms for hypoxia-inducible factor induction of EPO expression, and within erythroid progenitors EPOR engagement of canonical Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5), rat sarcoma/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAS/MEK/ERK), and phosphatidylinositol 3-kinase (PI3K) pathways. Contemporary genetic, bioinformatic, and proteomic approaches continue to uncover new clinically relevant modulators of EPO and EPOR expression, and EPO’s biological effects. This Spotlight review highlights such factors and their emerging roles during erythropoiesis and anemia.

scholarly journals Ob receptor in rabbit ovary and leptin in vitro regulation of corpora lutea

2004 ◽  
Vol 183 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Massimo Zerani ◽  
Cristiano Boiti ◽  
Danilo Zampini ◽  
Gabriele Brecchia ◽  
Cecilia Dall’Aglio ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Prostaglandin F2α ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Corpora Lutea ◽  
Positive Staining ◽  
Mitogen Activated Protein ◽  
Oxide Synthase ◽  
Camp And Cgmp

We studied leptin involvement in rabbit corpora lutea (CL) activity, and its post-transcriptional signalling pathway. The expression of leptin receptor (Ob-R) in rabbit ovary at day 9 of pseudopregnancy was evaluated by immunohistochemistry and Western blot analysis. The specificity of the Ob-R receptor antibodies was characterised by immunoprecipitation and competition with blocking peptide. Day 9 CL were incubated in vitro with leptin alone or with inhibitors of PLC (phospholipase C), PLD (phospholipase D), AC (adenylate cyclase), JAK (janus kinase), MAPK (mitogen-activated protein kinase) and both cAMP- and cGMP-specific PDE (phosphodiesterase). Prostaglandin F2α(PGF2α), PGE2 and progesterone levels were measured in the culture medium, while NOS (nitric oxide synthase) and cAMP- and cGMP- specific PDE activities were measured in CL tissue. Positive staining for Ob-R was found within the cytoplasm of large luteal cells of CL as well as in granulosa cells of follicles and oocytes. Immunoblots detected a band of about 99 kDa size in Ob-R immunoprecipitates from CL homogenates. This band was not detectable after pre-incubation of the primary antibody with the immunising leptin peptide. Leptin increased PGF2αand cAMP-specific PDE, decreased basal progesterone and did not affect PGE2 and NOS levels. Leptin used the JAK pathway in increasing PGF2α, and MAPK and cAMP-specific PDE in decreasing progesterone. This study supports a permissive luteolytic role for leptin in rabbit CL.

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