Antagonistic effects of lycopene on cadmium-induced hippocampal dysfunctions in autophagy, calcium homeostatis and redox.

Cadmium (Cd), a widely existed environmental contaminant, was shown to trigger neurotoxicity by regulating autophagy, ion homeostasis and redox. Lycopene (LYC) is a natural substance with potent antioxidant capacity. Nevertheless, little is known about i) the relationship of Cd-induced neurotoxicity and autophagy, ion homeostasis as well as redox in the hippocampus; ii) the role of LYC in the regulation of hippocampal autophagy, ionic balance and antioxidant capacity during Cd exposure. Therefore, this study sought to investigate the Cd exposure-induced hippocampal dysfunctions for neurotoxicity, and the preventive potential of LYC on the hippocampus impairment by reversing the dysfunctions during the exposure. In vivo study with mice model demonstrated that Cd exposure increased gene expression of a wide spectrum of autophagy-related gene (ATG) and gene regulating autophagy in hippocampus. This suggests the activation of hippocampal autophagy mediated by Cd. Cd exposure also decreased Ca2+-ATPase activity, thus increasing intracellular Ca2+ concentration in hippocampus, indicating the possibility that Cd-induced autophagy requires the Ca2+ signaling. Moreover, Cd exposure triggered redox stress in hippocampus cells, as antioxidant enzyme activities were decreased while oxidative productions were promoted. Cd exposure led to severe cytotoxicity in hippocampus cells. Of important note, all the hippocampal dysfunctions upon Cd exposure were reversed by LYC treatment to normal situations, and exposure-induced neurotoxicity was abrogated. The in vivo findings were recapitulated relevantly in the mouse hippocampal neuronal cell line, TH22. In all, the above data imply that LYC could be a potent therapeutic agent in treating Cd-triggered hippocampal dysfunctions and subsequent cell damage.

Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice.

OBJECTIVE: To study the inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. METHODS: Female mice were selected as experimental animals, and breast cancer tumor-bearing mouse models were established and then divided into groups A, B, C and D that respectively received saline, recombinant human endostatin, ginsenosides Rg3 and recombinant human endostatin combined with Rg3 intervention; 7 d, 14 d and 21 d after intervention, tumor tissue volume was measured; 21 d after intervention, mice were killed, tumor tissue was collected, and mRNA contents of angiogenesis molecules, invasion molecules, autophagy marker molecules and autophagy signaling pathway molecules were detected. RESULTS: At 7 d, 14 d and 21 d after intervention, tumor tissue volume of groups B, C and D was lower than that of group A, and tumor tissue volume of group D was lower than that of groups B and C; mRNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, mTOR, PI3K, Akt, JNK and Beclin-1 in tumor tissue of groups B, C and D were significantly lower than those of group A, and LC3-II/LC3-I was significantly higher than that of group A; mRNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, mTOR, PI3K, Akt, JNK and Beclin-1 in tumor tissue of group D were significantly lower than those of groups B and C, and LC3-II/LC3-I was higher than that of groups B and C. CONCLUSIONS: Endostar combined with ginsenoside Rg3 has stronger inhibiting effect on breast cancer tumor growth in tumor-bearing mice than single drug, and it can inhibit angiogenesis and cell invasion, and enhance cell autophagy.