Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although we recently reported that sudachitin (5,7,4'-trihydroxy-6,8,3'-trimethoxyflavone), a polymethoxyflavone isolated from the peel of Citrus sudachi, can induce apoptosis in human keratinocyte HaCaT cells, the mechanism underlying its action remains unclear. In this study, we explored the mechanisms underlying sudachitin-induced apoptosis in HaCaT cells. Sudachitin activated p38MAPK and inhibited ERK1/2, whereas another polymethoxyflavone, nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), activated ERK1/2. The p38MAPK inhibitor SB203580 significantly attenuated sudachitin-induced heat shock protein 27 phosphorylation, downstream of p38MAPK, and subsequent apoptosis, indicating that sudachitin induces apoptosis via the p38MAPK pathway. Additionally, sudachitin inhibited serum- and EGF-stimulated Raf-1-ERK1/2 activation, and blocked EGF-induced cell migration and proliferation in HaCaT cells. These results suggest that small structural differences in polymethoxyflavones can induce different cellular responses by altering the regulation of MAPK activities and that sudachitin may be a potential candidate for developing new drugs for skin diseases such as psoriasis.
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PMID:Sudachitin, a polymethoxyflavone from Citrus sudachi, induces apoptosis via the regulation of MAPK pathways in human keratinocyte HaCaT cells. 3151 96

The ongoing coronavirus disease 2019 (COVID-19) pandemic has affected millions worldwide and has been found to cause severe disease in patients with underlying comorbidities. In patients with known malignancies, in addition to constraints in routine healthcare, the risk of being susceptible to developing severe forms of the disease is of grave concern. While follow-up studies on survivors of the severe acute respiratory syndrome (SARS) 2003 outbreak revealed increased susceptibility to infections, tumours and cardiovascular abnormalities, recent studies implicating angiopoietin 2 in induction of inflammatory intussusceptive angiogenesis and diffuse alveolar damage in COVID-19 patients raises the possibility of progression of carcinogenetic processes in patients with known malignancies. Angiotensin converting enzyme-2 (ACE-2) mediated cellular entry of SARS-Cov2 leads to receptor shedding of ACE-2 and disrupts the renin angiotensin aldosterone axis (RAAS). This augments the pro-inflammatory and proliferative effects of RAAS, while attenuating the anti-inflammatory and anti-proliferative angiotensin 1-7 /Mas pathway. Angiopoietin-2, a molecule responsible for angiogenesis and cancer progression which corelates with tumour load in certain cancers, is upregulated by angiotensin 2-AT1 Receptor axis. Tumour microenvironment-comprising of various cells, blood vessels and extra cellular matrix which express the RAAS peptides-plays a key role in cancer initiation, progression and metastasis. Angiotensin 2 induces the formation of a desmoplastic environment, favouring cancer cell growth. ACE-2 downregulation causes bradykinin accumulation which may exert its proliferative action via mitogen activated protein kinase pathways which has established roles in cancers of breast and kidney. In addition to cytokine storm causing organ damage, acute inflammation in COVID-19 may also cause epithelial mesenchymal transition and heat shock protein 27 phosphorylation, both of which are key mediators in cancer signalling pathways. We hypothesise that SARS-Cov2, by impacting the RAAS and immune system, has the potential to cause tumour cell proliferation, apoptosis evasion and metastasis, thereby increasing the possibility of cancer progression in patients with known malignancies.
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PMID:Cancer progression in COVID-19: integrating the roles of renin angiotensin aldosterone system, angiopoietin-2, heat shock protein-27 and epithelial mesenchymal transition. 3308 49


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