Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a representative cyclopentenone prostaglandin, has many interesting biological effects. In this study, treatment of human breast cancer cells (MCF-7) with 15d-PGJ(2) led to accumulation of p53 protein. However, the p53 DNA binding and its transcriptional activity were significantly reduced. 15d-PGJ(2) directly modified p53 as verified by reacting recombinant p53 with biotinylated 15d-PGJ(2). 9,10-Dihydro-15-deoxy-Delta(12,14)-prostaglandin J(2) lacking the electrophilic alpha,beta-unsaturated functionality failed to inhibit p53 DNA binding as well as to modify p53. Moreover, by conducting an in vitro [(35)S]-labeled p53 translation assay, we identified cysteine 277 as a putative site of p53 modification by 15d-PGJ(2). The DNA-binding ability of a mutant p53 in which cysteine 277 was substituted by alanine was virtually unaffected by 15d-PGJ(2). Likewise, p53 binding activity of biotinylated 15d-PGJ(2) was abolished in mutant cells. In addition, cells expressing wild-type p53 exhibited p53 protein stability to a greater extent than mutant C277A cells. In conclusion, 15d-PGJ(2) can undergo nucleophilic addition to p53, presumably at the cysteine 277 residue, rendering this tumor suppressor less susceptible to proteasomal degradation.
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PMID:15-Deoxy-Delta(12,14)-prostaglandin J(2) stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue. 2020 57

Callistemon lanceolatus (Myrtaceae) has been utilized in folk medicine and its pharmacological properties are widely studied. Phytochemicals are effectively recognized as bases of pharmacologically potent drugs for the development of anticancer therapeutics. The free radical scavenging potential of numerous extracts of C. lanceolatus leaves, Hexane leaf extract (HLE), Chloroform leaf extract (CLE), Ethyl acetate leaf extract (ELE), Methanol leaf extract (MLE), and Aqueous leaf extract (ALE)) were determined by Biochemical assay. We evaluated the anticancer activity of C. lanceolatus leaves extracts against different human cancer cell lines viz liver cancer cells (HepG2), breast cancer cells (MCF7), and normal human embryonic kidney (HEK 293) cell line. The ELE and MLE extracts of C. lanceolatus leaves showed potential antiproliferative effects on HepG2 cells. On the basis of free radical scavenging potential and cytotoxicity studies, ELE and MLE extracts of C. lanceolatus leaves are further evaluated in detail for numerous biological activities. ELE and MLE extracts reduced the cell growth, ROS generation, lowering the potential of cell migration and inhibits the metastatic activity in HepG2 cell lines. ELE and MLE extracts treated HepG2 cells showed down-regulation of STAT3 and up-regulation of p53 and inhibition of cdk2 and cyclin A activity. Phytochemicals analysis have shown that the ELE and MLE possess some anticancer compounds like 4-Fluoro-2-trifluoromethylbenzoic acid, neopentyl ester; fumaric acid, di(pent-4-en-2-yl) ester; 2,3-Dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one and 2-Furancarboxaldehyde,5-(hydroxymethyl). Molecular docking results demonstrate that interactions of compounds present in ELE and MLE extracts with the SH2 domain of STAT3, might be responsible for their inhibitory effects. We have further concluded that the ELE and MLE extracts of C. lanceolatus arrests the cells at S and G2/M phase and subsequently induced cell death by regulating the DNA damage in HepG2 cells.
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PMID:Antioxidant and apoptotic effects of Callistemon lanceolatus leaves and their compounds against human cancer cells. 3011 88

Neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery is the standard of care for patients with Locally Advanced Rectal Cancer (LARC). Current selection for nCRT is based on clinical criteria regardless of any molecular marker. Pharmacogenomics may be a useful strategy to personalize and optimize nCRT in LARC. This review aims to summarize the most recent and relevant findings about the role of germline and somatic pharmacogenomics in the prediction of nCRT outcome in patients with LARC, discussing the state of the art of their application in the clinical practice. A systematic literature search of the PubMed database was completed to identify relevant English-language papers published up to January 2020. The chemotherapeutic backbone of nCRT is represented by fluoropyrimidines, mainly metabolized by DPD (Dihydro-Pyrimidine Dehydrogenase, DPYD). The clinical impact of testing DPYD*2A, DPYD*13, c.2846A > T and c.1236G > A-HapB3 before a fluoropyrimidines administration to increase treatment safety is widely acknowledged. Other relevant target genes are TYMS (Thymidylate Synthase) and MTHFR (Methylene-Tetrahydro-Folate Reductase), whose polymorphisms were mainly studied as potential markers of treatment efficacy in LARC. A pivotal role of a TYMS polymorphism in the gene promoter region (rs34743033) was reported and was pioneeringly used to guide nCRT treatment in a phase II study. The pharmacogenomic analysis of other pathways mostly involved in the cellular response to radiation damage, as the DNA repair and the activation of the inflammatory cascade, provided less consistent results. A high rate of somatic mutation in genes belonging to PI3K (Phosphatidyl-Inositol 3-Kinase) and MAPK (Mitogen-Activated Protein Kinase) pathways, as BRAF (V-raf murine sarcoma viral oncogene homolog B1), KRAS (Kirsten Rat Sarcoma viral oncogene homolog), NRAS (Neuroblastoma RAS viral (v-ras) oncogene homolog), PIK3CA (Phosphatidyl-Inositol-4,5-bisphosphate 3-Kinase, Catalytic Subunit Alpha), as well as TP53 (Tumor Protein 53) was reported in LARC. Their pharmacogenomic role, already defined in colorectal cancer, is under investigation in LARC with promising results concerning specific somatic mutations in KRAS and TP53, as predictors of tumor response and prognosis. The availability of circulating tumor DNA in plasma may also represent an opportunity to monitor somatic mutations in course of therapy.
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PMID:Germline and Somatic Pharmacogenomics to Refine Rectal Cancer Patients Selection for Neo-Adjuvant Chemoradiotherapy. 3262 92