Oncotarget: A potent inhibitor of MAP-kinase is mediated by HIF-1α

Oncotarget published "Novel 3-(3, 5-difluoro-4-hydroxyphenyl)-1-(naphthalen-2-yl) prop-2-en-1-one as a potent inhibitor of MAP-kinase in HeLa cell lines and anti-angiogenic activity is mediated by HIF-1α in EAC animal model" which reported that the authors synthesized chalcone bearing naphthalene compound d1, and on the basis of 1H-NMR, 13C NMR, and LC-MS data they had specified the structure of the synthesized compound.

The resultant compound d1 was assessed for their antiproliferative action against human cancer cell lines.

The IC50 range was estimated at 5.58 to 11.13 μM shows that compound d1 had remarkable anticancer activity on HeLa cell lines.

The authors depicted the in-vivo effects of tumor advancement and the antiangiogenic activity of d1 in the EAC animal model. Tumor growth had inhibited and without symptoms the longevity of EAC containing mice expanded by the treatment of d1. Inhibition of nuclear transcriptional factor HIF-1α in EAC cells and finally it also inhibited phosphorylation of downstream signaling proteins such as ERK1/2, p38, and JNK in HeLa cells.

The present Oncotarget investigation uncovered that d1 indicated noteworthy tumor-repressing abilities much less concentration in in-vitro and in-vivo recommended that compound d1 as the potent anticancer medication.

The present Oncotarget investigation uncovered that d1 indicated noteworthy tumor-repressing abilities much less concentration in in-vitro and in-vivo recommended that compound d1 as the potent anticancer medication.

Dr. Shankar Jayarama from Davanagere University said, "Cancer is a death-defying disease that causes a genuine medical issue around the world."

Apoptosis is programmed cell death and the most extensively investigated mode of cell death that occurs in different pathological and physiological situations .

Apoptosis plays an important role in the control of normal development, aging, and tissue homeostasis by facilitating the removal of unwanted, damaged, infected cells, or mutated cells.

Apoptosis is an energy-dependent manner in which the typical morphological changes occur; it includes cell membrane blebbing, cell shrinkage, and chromatin condensation, the formation of the cytoplasmic vacuole, and DNA fragmentation.

Figure 9: (A) Western blots analysis for anti-angiogenic action on d1 in Cytosolic extract from EAC cells. (B) Anti-angiogenic action on d1 in nuclear extract. (C) Graphical representation of cytosolic expression level in EAC cells. (D) Graphical representation of cytosolic expression level in EAC cells. Statistical significance was expressed as ^***P < 0.0001 by using one-way ANOVA.

The cell fragments generated by apoptosis are taken up and eliminated by neighbouring cells through phagocytosis.

Binding of explicit ligands/development factors to its receptor instigates receptor dimerization and autophosphorylation, bringing about the enactment of the intracellular signaling pathway, which manages cell separations, development, relocation, and apoptosis.

The Jayarama Research Team concluded in their Oncotarget Research Output, "the present study demonstrated that compound d1 is a very potent anti-angiogenic compound that inhibits the growth of EAC cells in-vivo. These inhibitory effects may be related to the suppression of transcriptional factor HIF-1α nuclear translocation. HIF-1α is accountable for inhibition of hypoxic up-regulation of VEGF gene expression, resulting in decreased ascites volume and thereby inhibiting the tumor growth which is angiogenic reliant and also inhibiting the phosphorylation of downstream signaling components such as ERK, p38, and JNK of the MAPK pathway. It is also evident that inhibition of the downstream signaling pathway was due to the binding of compound d1 to VEGFR, preventing the binding of other growth factors. Such active compound d1 prove to be potential anti-angiogenic drugs that could be further developed and translated into a therapeutic regime for the treatment of various human cancers."

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DOI - https://doi.org/10.18632/oncotarget.27836

Full text - https://www.oncotarget.com/article/27836/text/

Correspondence to - Shankar Jayarama - sankkar.bio@gmail.com

Keywords - novel chalcone, Bcl2, caspase 3, BAX, receptor tyrosine kinase inhibitor

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