Functional polymorphisms in NR3C1 are associated with gastric cancer risk in Chinese population
Authors: Gu, Yayun; Deng, Bin; Kong, Jing; Yan, Caiwang; Huang, Tongtong; Yang, Jianshui; Wang, Yan; Wang, Tianpei; Qi, Qi; Jin, Guangfu; Du, Jiangbo; Ding, Yanbing; Liu, Li
Recently promoter of NR3C1 has been found to be high methylated in gastric cancer tissues which might be involved in the initiation of gastric carcinoma development. To test whether the variants in NR3C1 could modify the risk of gastric cancer, we evaluated the association between four SNPs (rs6194, rs12521436, rs33388 and rs4912913) in NR3C1 and gastric cancer risk in a case-control study with 1,113 gastric cancer cases and 1,848 cancer-free controls in a Chinese population. We found a significant association between rs4912913 and gastric cancer risk (OR=1.18, 95% CI=1.05-1.33, P=5.49x10(-3)). We also observed that the A-allele of rs12521436 and rs33388 were significantly associated with a decreased risk of gastric cancer (OR=0.84, 95% CI=0.76-0.94, P=2.78x10(-3); OR=0.85, 95% CI=0.75-0.97; P=0.018). Finally, we made a joint effect analysis of rs12521436, rs33388 and rs4912913 on risk of gastric cancer (P-Trend=2.83x10(-5)). These findings indicate that the variants rs4912913, rs33388 and rs12521436 of NR3C1 may contribute to gastric cancer susceptibility.
Quantum chemical studies, vibrational analysis, molecular dynamics and docking calculations of some ent-kaurane diterpenes from Annona vepretorum: a theoretical approach to promising anti-tumor molecules
Authors: Costa, Renyer A.; da Silva, Jonathas Nunes; Oliveira, Kelson M. T.; Dutra, Livia M.; Costa, Emmanoel, V
Diterpenes are a class of secondary metabolites that attract much attention due to the numerous biological activities presented, such as antimicrobial, antiviral, hypoglycemic, larvicidal, and antitumor. In the present study, four ent-kaurane diterpenes isolated from Annona vepretorum were analyzed through a DFT theoretical approach using the B3LYP exchange-correlation functional with 6-311G (2d, p) basis set, which allowed to obtain optimized geometry of the structures, highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO), MEPS analysis, and vibrational wavenumbers. The analysis of the HOMO-LUMO energy gaps and reactive descriptor indices values allowed us to verify that the structures present a differentiated reactivity, indicating a differentiated activity. The comparative IR studies, allied to potential energy distribution calculation, revealed several characteristic vibrations that characterize the ent-kaurane skeleton, besides enabling the existence of intermolecular H-bonds through dimers formation. By molecular dynamic simulations, the interactions between diterpenes atoms and water, methanol, and chloroform were simulated, which enable us to analyze the stability of the studied structures in different solvated media and the best sites to form H-bonds. In addition, the stability of intramolecular H-bonds was evaluated. Guided by the in vitro cytotoxicity presented by the investigated diterpenes, molecular docking calculations were performed with the key enzymes NR3C1 and with rat-type II adenylyl cyclase C2 (ACC2) domain, revealing good interactions with the active site of the tested enzymes, justifying the previous experimental results.