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Keywords = puromycin reaction

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13 pages, 4150 KB  
Article
p53-Dependent Apoptotic Effect of Puromycin via Binding of Ribosomal Protein L5 and L11 to MDM2 and Its Combination Effect with RITA or Doxorubicin
by Ji Hoon Jung, Hyemin Lee, Ju-Ha Kim, Deok Yong Sim, Hyojin Ahn, Bonglee Kim, Suhwan Chang and Sung-Hoon Kim
Cancers 2019, 11(4), 582; https://doi.org/10.3390/cancers11040582 - 24 Apr 2019
Cited by 28 | Viewed by 7782
Abstract
Among ribosomal proteins essential for protein synthesis, the functions of ribosomal protein L5 (RPL5) and RPL11 still remain unclear to date. Here, the roles of RPL5 and RPL11 were investigated in association with p53/p21 signaling in the antitumor effect of puromycin mainly in [...] Read more.
Among ribosomal proteins essential for protein synthesis, the functions of ribosomal protein L5 (RPL5) and RPL11 still remain unclear to date. Here, the roles of RPL5 and RPL11 were investigated in association with p53/p21 signaling in the antitumor effect of puromycin mainly in HCT116 and H1299 cancer cells. Cell proliferation assays using 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays and colony formation assays, cell cycle analysis, Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were performed in cancer cells. Puromycin exerted cytotoxic and anti-proliferative effects in p53 wild-type HCT116 more than in p53 null H1299 cells. Consistently, puromycin increased sub-G1, cleaved Poly (ADP-ribose) polymerase (PARP), activated p53, p21, and Mouse double minute 2 homolog (MDM2), and attenuated expression of c-Myc in HCT116 cells. Notably, puromycin upregulated the expression of RPL5 and RPL11 to directly bind to MDM2 in HCT116 cells. Conversely, deletion of RPL5 and RPL11 blocked the activation of p53, p21, and MDM2 in HCT116 cells. Also, puromycin enhanced the antitumor effect with reactivating p53 and inducing tumor apoptosis (RITA) or doxorubicin in HCT116 cells. These findings suggest that puromycin induces p53-dependent apoptosis via upregulation of RPL5 or RPL11 for binding with MDM2, and so can be used more effectively in p53 wild-type cancers by combination with RITA or doxorubicin. Full article
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21 pages, 4326 KB  
Review
Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions
by George P. Dinos, Constantinos M. Athanassopoulos, Dionissia A. Missiri, Panagiota C. Giannopoulou, Ioannis A. Vlachogiannis, Georgios E. Papadopoulos, Dionissios Papaioannou and Dimitrios L. Kalpaxis
Antibiotics 2016, 5(2), 20; https://doi.org/10.3390/antibiotics5020020 - 3 Jun 2016
Cited by 127 | Viewed by 24782
Abstract
Chloramphenicol (CAM) is the D-threo isomer of a small molecule, consisting of a p-nitrobenzene ring connected to a dichloroacetyl tail through a 2-amino-1,3-propanediol moiety. CAM displays a broad-spectrum bacteriostatic activity by specifically inhibiting the bacterial protein synthesis. In certain but important [...] Read more.
Chloramphenicol (CAM) is the D-threo isomer of a small molecule, consisting of a p-nitrobenzene ring connected to a dichloroacetyl tail through a 2-amino-1,3-propanediol moiety. CAM displays a broad-spectrum bacteriostatic activity by specifically inhibiting the bacterial protein synthesis. In certain but important cases, it also exhibits bactericidal activity, namely against the three most common causes of meningitis, Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Resistance to CAM has been frequently reported and ascribed to a variety of mechanisms. However, the most important concerns that limit its clinical utility relate to side effects such as neurotoxicity and hematologic disorders. In this review, we present previous and current efforts to synthesize CAM derivatives with improved pharmacological properties. In addition, we highlight potentially broader roles of these derivatives in investigating the plasticity of the ribosomal catalytic center, the main target of CAM. Full article
(This article belongs to the Special Issue Inhibitors of the Translational Apparatus)
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