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Objectives: To examine the expression of N-Myc downstream regulated gene 2 (NDRG2) in the cryptorchid testes and its potential association with germ cell apoptosis in a rat model of cryptorchidism. Methods: Groups of pubertal Sprague-Dawley rats were subjected to surgical procedure for the induction of experimental unilateral cryptorchidism. The weight of the abdominal and scrotal testes was measured and their apoptotic cells and NDRG2 expression were examined longitudinally by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, immunohistochemistry, and immunofluorescence analyses. The expression of NDRG2 and p53 in the purified germ cells and Leydig cells was determined by Western blot assay. Results: Compared with the control scrotal testes, the mean weights of the abdominal testes were significantly reduced at 7 and 14 days after surgery, accompanied by significantly increased numbers of apoptotic germ cells. Although the NDRG2 expression was detected in Leydig cells and spontaneous apoptotic germ cells in the scrotal testes, it was significantly upregulated predominately in apoptotic spermatocytes and round spermatids in the abdominal testes. However, the NDRG2 expression was downregulated in Leydig cells in the abdominal testes. Western blot analysis revealed that the expression of NDRG2 and p53 was upregulated significantly in purified germ cells 7 days after surgery, whereas NDRG2 was downregulated in the purified Leydig cells from the abdominal testes 7 and 14 days after surgery. Conclusions: The upregulated expression of NDRG2 was associated with germ cell apoptosis in the cryptorchid testes, suggesting that the NDRG2 may be a positive regulator for germ cell apoptosis in rat cryptorchidism. [Copyright &y& Elsevier]

Abstract: This study is the first to investigate Calebin-A, a natural compound present in Curcuma longa, which inhibits cell growth and induce apoptosis in SGC7901/VINCRISTINE cells, a multidrug resistant (MDR) human gastric adenocarcinoma cell line. Our data suggest the drug efflux function of P-glycoprotein was inhibited by Calebin-A treatment, while the expression level of P-glycoprotein was not affected. Additionally, co-treatment of Calebin-A and vincristine resulted in a remarkable reduction in S phase and G2/M phase arrest in SGC7901/VINCRISTINE cells. Calebin-A was also found to modulate the activities of mitogen-activated protein kinase (MAPK) family members, which includes decreased c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and increased protein kinase of 38 kDa (p38) activity. These results suggest that Calebin-A might be an effective compound for the treatment of human gastric and other MDR cancers. [Copyright &y& Elsevier]