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Brucine is an alkaloid derived from the seeds of Strychnos nux-vomica Linn. which have long been used as a traditional medicine for the treatment of hepatocellular carcinoma (HCC) in China. HCC prognosis can be greatly influenced by metastasis. There has thus far been little research into brucine as a source of anti-metastasis activity against HCC. In this study, we revealed that brucine dramatically repressed HepG2 and SMMC-7721 HCC cell migration with few cytotoxic effects. Hypoxia inducible factor 1 (HIF-1) is a key transcription factor mediating cell migration and invasion. Brucine suppressed HIF-1-dependent luciferase activity in HepG2 cells. The transcriptions of four known HIF-1 target genes involved in HCC metastasis, i.e., fibronectin, matrix metallopeptidase 2, lysyl oxidase, and cathepsin D, were also attenuated after brucine treatment. Experiments in vivo showed that an intraperitoneal injection of 5 and 15 mg/kg of brucine resulted in dose-dependent decreases in the lung metastasis of H22 ascitic hepatoma cells. Moreover, a dosage of brucine at 15 mg/kg exhibited very low toxic effects to tumor-bearing mice. Consistently, brucine downregulated expression levels of HIF-1 responsive genes in vivo. Our current study demonstrated the capacity of brucine in suppressing HCC cell migration in vitro and lung metastasis in vivo. The inhibition of the HIF-1 pathway is implicated in the anti-metastasis activity of brucine., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

We found that cluster determinant 36 (CD36) gene is up-regulated in essential hypertension (EH) patients in our former research, but the association between CD36 gene variations and EH has not yet been clearly demonstrated. The relationship between CD36 gene single nucleotide polymorphisms (SNPs) and EH in the northeastern Han Chinese was examined in the present study through direct sequencing and genotype-detection. A total of 589 unrelated northeastern Han Chinese including 276 with EH and 313 controls were studied. SNPs in exon 7, exon 13 and intron 4 were detected using PCR-sequencing. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). +216T/C, +273A/G, +132C/T, +217T/C, +212T/G and +233T/C polymorphisms were identified. Distributions of genotypes AA, GA and GG of +273A/G polymorphism were significantly different between EH group and the control group (χ2: 9.056, p=0.011) and G allelic frequency was higher in EH (p=0.006, OR=1.629, 95% CI [1.224-2.168]). Logistic regression analysis showed that +273A/G polymorphism was closely associated with blood pressure (BP) after adjusting for ages. When subclassified by sex, the genotype distribution of +273A/G (p=0.011) and allelic frequency of G allele (p=0.006) were significantly different between EH participants and controls in males, but not in females. Subgroup analysis performed by body mass index (BMI) suggested that the genotype distribution of +273A/G and allelic frequency were significantly different in non-obese group and non-obese men, but the associations were not significant (non-obese group: p=0.016, OR=1.664, 95% CI [1.459-2.409]; non-obese men: p=0.073, OR=1.898, 95% CI [1.033-3.487]). +273A/G polymorphism in CD36 gene was associated with EH, and +273G could be an independent predictor., (Copyright © 2013 Elsevier B.V. All rights reserved.)