ABSTRACT
The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to ß-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.
Subject(s)
Adenocarcinoma of Lung , Antineoplastic Agents , Cisplatin , Nasopharyngeal Neoplasms , Adaptor Proteins, Signal Transducing , Adenocarcinoma of Lung/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Bufanolides , Calmodulin-Binding Proteins , Cell Line, Tumor , Cisplatin/pharmacology , Cisplatin/therapeutic use , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Myosin Heavy Chains , Myosins/metabolism , Nasopharyngeal Neoplasms/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Transcription Factors/metabolism , Ubiquitin-Specific Peptidase 7 , beta Catenin/metabolismABSTRACT
A novel and reliable method for the direct preparation of 2,2-dihalo-N-phenylacetamides is reported. The key transformation involves the cleavage of a carbon-carbon bond in the presence of DIB and a Lewis acid as the halogen source, and thus this method significantly expands the value of DIB as a unique and powerful tool in chemical synthesis. This protocol not only adds a new aspect to reactions that use other hypervalent iodine reagents but also provides a wide space for the synthesis of disubstituted acetamides.
ABSTRACT
1-Carbamoyl-2-oxopropyl acetate derivatives were synthesized through an acetoxylation process to methylene with the aid of (diacetoxyiodo)benzene (DIB) as the oxidant. Not only mild reaction conditions, but also excellent yields and good substrate scope make the present protocol potentially useful in organic synthesis.
ABSTRACT
In the title complex, [La(C(6)H(4)NO(3))(C(2)O(4))(H(2)O)(2)](n), the La(III) ion is coordinated by eight O atoms from two 2-oxido-pyridinium-3-carboxyl-ate ligands, two oxalate ligands and two water mol-ecules in a distorted bicapped square-anti-prismatic geometry. The carboxyl-ate groups link adjacent La(III) ions, forming two-dimensional layers that are further linked by N-Hâ¯O and O-Hâ¯O hydrogen bonds.
