ABSTRACT
BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder. Oxidative stress is a main modulator in the advancement of PD. This investigation aimed to evaluate the relations between serum trace elements, vitamin C, ferritin, transferrin, Nitrite Oxide (NOx) and Peroxynitrite (PrN) concentrations and clinical parameters in patients with PD. METHODS: Serum concentrations of variables were measured in 75 PD patients and 75 healthy subjects from Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran between Feb 2016 and Sep 2018. Receiver Operating Characteristic (ROC) analysis was performed to examine incremental diagnostic value of vitamin C, NOx, and PrN in the study groups. RESULTS: Mean serum NOx (35.81±5.16 vs. 11.27±3.59 mol/L, P<0.001) and PrN (15.78±4.23 vs. 9.62±4.57 mol/L, P= 0.004) were markedly higher in patient group versus healthy individuals. Significant differences were also observed in the serum levels of vitamin C (P<0.001), copper (Cu) (P<0.001), Iron (Fe) (P=0.003), and Zinc (Zn) (P<0.001) between patients with PD and healthy subjects. Nevertheless, the serum levels of Se (P=0.515), ferritin (P=0.103), and transferrin (P=0.372) were not statistically significant between the study groups. ROC analysis has revealed a diagnostic ability of serum vitamin C levels for PD with an area under ROC curve of ≥0.7 (P<0.05) and relatively high sensitivity and specificity. CONCLUSION: Serum levels of NOx and PrN are significantly higher in patients with PD. In additions, serum vitamin C levels have a diagnostic value as a biomarker. Further studies are required with larger sample size to provide more detailed information about the cognitive profile of participants and the outcome measures.
ABSTRACT
BACKGROUND: Piperine is a natural compound obtained from the Piper nigrum that exhibits anti-proliferative and anti-cancer activity in cancer cell lines. We analyzed the cytotoxic effect of piperine combined with cisplatin compound in the human MCF-7 breast cancer cell line and the underlying mechanism. METHODS: The present in vitro study was performed on MCF-7 cell line in Jahrom University of Medical Sciences between, Jahrom, Iran from 2016 to 2017. Cultured MCF-7 cells were seeded into four groups: a control group (untreated group), a group treated with cisplatin, a group treated with piperine and a group treated with cisplatin and piperine. Cell viability was analyzed using the MTT assay method. Flow c-ytometric analysis was investigated for apoptosis. The mRNA and protein expression of the apoptotic regulators p53, Bcl-2, Bax, caspase 3 and caspase 9 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis. RESULTS: Piperine (20 and 30 µM) in combination with cisplatin (5, 10 and 15 µM) for 24 h synergistically inhibited cell viability of MCF-7 breast cancer cells more than piperine and cisplatin used alone. Synergistic anti-breast cancer activities cisplatin (5 µM) and piperine (20 µM) were via inducing apoptosis. Piperine (20 µM) and cisplatin (5 µM) for 24 h induce apoptosis strongly through reduction of Bcl-2 and increase of caspase 3, p53, caspase 9, and Bax. CONCLUSION: Piperine in combination with cisplatin could trigger p53-mediated apoptosis more effective than cisplatin alone in MCF-7 breast cancer cells, reducing the toxic dose of cisplatin used in cancer chemotherapy.
ABSTRACT
Cisplatin is widely used as an anticancer drug in chemotherapy of human cancers. In the field of cancer therapy, nanoparticles modified with biocompatible copolymers are suitable vehicles to effectively deliver smaller doses of hydrophobic drugs such as cisplatin in the body. In this study, we investigated whether cisplatin-loaded iron oxide nanoparticles (IONPs) modified with chitosan can exert cytotoxic effects in the human breast cancer cell line MDA-MB-231. IONPs was synthesized using eucalyptus leaf extract as a reducing and stabilizing agent. MDA-MB-231 cells were treated with different concentrations of cisplatin, cisplatin-IONPs and cisplatin-IONPs-chitosan for 24 h. Apoptosis was confirmed by flow cytometry, whereas The mRNA and protein expression of pro- and anti-apoptotic molecules were measured using Real time RT-PCR and western blotting. Treatment with both cisplatin-IONPs and cisplatin-IONPs-chitosan showed a significantly higher cytotoxic effect in comparison to the free drug alone in MDA-MB-231 cells. The levels of apoptosis in cells treated with a combination of cisplatin-IONPs-chitosan were significantly higher compared with cisplatin-IONPs and cisplatin alone. The results of this study showed that the interaction between cisplatin and iron oxide nanoparticles modified with chitosan could enhance responsiveness to cisplatin in breast cancer cells.
