Gemini curcumin inhibits 4T1 cancer cell proliferation and modulates the expression of apoptotic and metastatic genes in Balb/c mice model.

BACKGROUND: Despite the attractive anti-cancer effects, poor solubility and low bioavailability have restricted the clinical application of Curcumin. Recent findings show that Gemini nano-curcumin (Gemini-Cur) significantly improves the cellular uptake of Curcumin and its anti-cancer effect in tumor cells. Here, we aimed to assess the suppressive effect of Gemini-Cur on 4T1 breast cancer cells in vitro and, subsequently, in BALB/c mouse models. MATERIALS AND METHODS: Fluorescence microscopy was employed to visualize cellular uptake and morphological changes of 4T1 cells during treatment with Gemini-Cur and void curcumin. MTT and annexin V/FITC assays were performed to study the toxic effect of Gemini-Cur on mouse cancer cells. For in vivo studies, BALB/c tumor-bearing mice were used to evaluate the inhibitory effect of Gemini-Cur in comparison with mice receiving free Curcumin and nanoparticles. RESULTS: Our data showed that Gemini-Cur enters the cells and inhibits proliferation in a time- and dose-dependent manner. Annexin V/FITC confirmed apoptotic effect on 4T1 cells. In vivo studies also illustrated that tumor growth is suppressed in Gemini-Cur treated mice rather than controls. Expression studies demonstrated the modulation of apoptotic and metastatic genes, including Bax, Bcl-2, MMP-9, VEGF, and COX-2 in treated mice. CONCLUSION: In conclusion, these data demonstrate the promising anti-cancer properties of Gemini-Cur on mice models. However, further studies at molecular and cellular levels are required to conclude this therapeutic advantage.

Intra­LPGi microinjection of glutamate receptors antagonists abolish 17ß­estradiol­induced analgesic effect in the ovariectomized rats.

This study was designed to investigate a possible interaction between 17ß­estradiol and glutamate receptors of the paragigantocellularis lateralis (LPGi) nucleus on pain coping behavior using the formalin test in ovariectomized (OVX) rats. The results showed that intra­LPGi injection of 17ß­estradiol declined flexing behavior in both phases of the formalin test. Still, it only diminished the late phase of licking behavior in the OVX rats. NMDA receptor antagonist, AP5, reversed the analgesic effect of 17ß­estradiol on flexing behavior in both phases of the formalin test in the OVX rats. The 17ß­estradiol­induced anti­nociceptive effect on the flexing duration was prevented by CNQX (AMPA receptor antagonist) only in the early phase of the formalin test in the OVX rats. AP5 and CNQX reduced the anti­nociceptive effect of 17ß­estradiol in the late phase, but not the early phase of licking response in the OVX rats. These results suggested: (i) The intra­LPGi injection of 17ß­estradiol is satisfactory in producing modest analgesia on the formalin­induced inflammatory pain in the OVX rats; (ii) Co­treatment of glutamate receptors (NMDA and AMPA) antagonists and 17ß­estradiol in the LPGi nucleus decrease the analgesic effect of 17ß­estradiol in the OVX rats; (iii) There is a possible association between 17ß­estradiol and glutamate receptors of the LPGi nucleus on pain coping behavior in the OVX rats.

Attenuation of phosphorylated connexin-43 protein levels in diabetic rat heart by regular moderate exercise.

BACKGROUND: High blood glucose levels increase the ratio of phosphorylated to non-phosphorylated connexin-43 amounts, which leads to the decomposition of the hyperphosphorylated connexin-43. This can cause heart arrhythmia in diabetic patients. Considering the effective role of exercise in diabetic patients, and because there are few studies regarding the effect of exercise on phosphorylated connexin-43 protein levels, in the present study the impact of different periods of moderate regular exercise on phosphorylated Connexion-43 levels were examined. METHODS: Sixty (60) male Wistar rats (300 ± 50 g) were randomly divided into six groups (n = 10). A week after induction of diabetes by injection of streptozotocin, one hour treadmill exercise, 5 days a week with 22 (m/min) speeds was undertaken. Left ventricles of hearts were isolated and immediately frozen. Finally, phosphorylated connexin-43 protein levels were measured by ELISA method. RESULTS: The means of blood glucose levels were significantly decreased (P < 0/05) by increasing days of exercise. The means of blood glucose levels were significantly decreased (P < 0/05) by increasing days of exercise. Regular moderate exercise reduced the connexin-43 levels by increasing days of exercise (P < 0.01). CONCLUSION: It is concluded that regular moderate exercise reduces the amount of phosphorylated connexin-43 protein levels in the ventricular myocardium, by reducing blood glucose levels. This can result in partial inhibition of cardiac arrhythmia observed in diabetic patients. This research was done in Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.