Antioxidant Supplementation during Glioma Therapy: Friend or Foe?

Gliomas which are one of the most common types of primary brain tumors are originated from glial cells. Type of tumor and tumor location are the most important factors to determine the treatment options. The treatment options might be surgery, radiation therapy, chemotherapy, targeted therapies, and experimental clinical studies. Especially, in course of chemotherapy and radiotherapy, antioxidant levels decrease. Antioxidants fight against the oxidants’ negative effects, which include cell damage, oxidative stress, and so on. Recent years, some researchers present that the antioxidant using could be harmful in some cases. A growing body of evidence suggests that antioxidant supplementation might increase the mortality. In this chapter, an overview of antioxidants and their functions has been presented to introduce researchers to the changes and effects of the antioxidants in glioma treatment. The evidence-based studies have been summarized. These experimental studies are important to understand the right option for the patient and transfer the solution from bench to bed

In vitro učinci selena na stanične linije humanog glioblastoma multiforme: preliminarno istraživanje

Glioblastoma multiforme (GBM) is caused by the central nervous system-derived glial cells, and represents the most common (50%-60%) form of primary brain tumors. The aim of this study was to investigate the in vitro effects of selenium on human GBM cells. In the present study, GMS-10 and DBTRG-05MG human GBM cell lines were used as a model to examine selenium entering the cell, cell proliferation, cytotoxicity, DNA fragmentation and Ki-67 protein expression in selenomethionine treated and non-treated groups. Seleno-L-methionine (SeMet) as the organic source of selenium exerted effects on cell proliferation and cytotoxicity, as assessed with WST-1 and lactate dehydrogenase (LDH) tests, respectively. Apoptosis was assessed by DNA fragmentation with an enzyme-linked immunosorbent assay. Ki-67 protein expression was determined by Western blotting, while selenium measurements were performed in the supernatants and lysates by using Graphite Furnace Atomic Absorption Spectrometry. Th is is the first study to examine the effects of SeMet on cell proliferation and death in GMS-10 and DBTRG-05MG cells. Both GBM cell lines responded to SeMet in a dose- and time-dependent manner. WST-1 test showed that low-dose SeMet treatment (50 and 100 μM) increased cell proliferation. Analysis of intracellular SeMet levels by using AAS showed results consistent with viability and cytotoxicity tests. SeMet treatment for 72 h caused increased DNA fragmentation in both cell lines. In conclusion, our results suggest that SeMet induces cell death at high doses, while increasing cell proliferation at low doses. In the view of the data obtained in this investigation, further studies focusing on the possibility of using SeMet against different types of GBM and in combination with prospect synergic compounds are considered to be worthwhile.Glioblastom multiforme (GBM) uzrokuju glijalne stanice podrijetlom iz središnjega živčanog sustava i to je najčešći (50%-60%) oblik primarnog tumora mozga. Cilj ovoga istraživanja bio je ispitati in vitroučinke selena na stanice humanog GBM. Rabili smo stanične linije GMS-10 i DBTRG-05MG humanog GBM kao model za ispitivanje ulaska selena u stanicu, stanične proliferacije, citotoksičnosti, fragmentacije DNA i izraženosti proteina Ki-67 u skupini tretiranoj selenometioninom i skupini bez takve obrade. Seleno-L-metionin (SeMet) kao organski izvor selena utjecao je na staničnu proliferaciju i citotoksičnost, što je procijenjeno pomoću testova WST-1 odnosno laktat dehidrogenaze (LDH). Apoptoza je procijenjena fragmentacijom DNA testom ELISA. Izražajnost proteina Ki-67 utvrđena je Western blotingom, dok su mjerenja selena provedena u supernatantima, a lizati primjenom GFAAS. Ovo je prvo istraživanje u kojem su se ispitivali učinci SeMet na staničnu proliferaciju i smrt u stanicama GMS-10 i DBTRG-05MG. Obje stanične linije GBM pokazale su o dozi i vremenu ovisan odgovor na SeMet. Test WST-1 pokazao je da je tretman niskom dozom SeMet (50 i 100 μM) pove-ćao proliferaciju stanica. Rezultati analize unutarstaničnih razina SeMet pomoću AAS bili su sukladni rezultatima testova stanične životnosti i citotoksičnosti. Tretman pomoću SeMet kroz 72 h uzrokovao je povećanu fragmentaciju DNA u objema staničnim linijama. U zaključku, naši rezultati ukazuju na to da SeMet u visokim dozama izaziva staničnu smrt, dok u niskim dozama povećava staničnu proliferaciju. U svjetlu podataka dobivenih u ovom istraživanju smatramo da bi bilo opravdano daljnja istraživanja usredotočiti na moguću primjenu SeMet kod različitih tipova GBM i u kombinaciji s mogućim sinergističnim spojevima

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

BACKGROUND: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells. METHODS: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549) and p53-null (H1299) cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels. RESULTS: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC(50)) values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 μM and 100 μM. CONCLUSION: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells

Relationship of Wnt pathway activity and organ involvement in scleroderma types

Objective Scleroderma (SSc) is a chronic inflammatory autoimmune disease characterized by fibrosis in the skin and internal organs. In SSc, the heart, lung, kidney, gastrointestinal (GIS) system, muscle, and peri-articular structures are damaged. There is no study of the relationship between SSc type, stage, pathogenesis, organ involvement, and Wnt signaling. In this study, we aimed to show the relationship of the Wnt gene family and antagonists in SSc subtypes and different organ involvement. Methods Eighty-five SSc patients and 77 controls were included in this study. The gene expressions and protein levels of the Wnt family and antagonists were analyzed from blood samples. The relationship between these parameters and disease stage, type, and organ involvement were evaluated. Results Wnt-1, Wnt-10b, Wnt-2, and Wnt-6 gene expressions are increased and Axin-2, DKK-1, and Kremen protein expressions are decreased in SSc. Wnt-3a and Wnt-10a gene expressions are increased in generalized SSc compared to limited SSc. Wnt-1, Wnt-2 gene expressions are increased significantly in pulmonary arterial hypertension (PAH)(+) SSc compared to PAH(-) SSc. There was a positive correlation between the modified Rodnan skin score and Wnt-2 in SSc. There was a significant positive correlation between GIS involvement score and Wnt-1, Wnt-2, Wnt-4, Wnt-8a, Wnt-9b in SSc. Conclusion Wnt-1 and Wnt-2 were found higher in scleroderma and organ involvement. They may play a role in the pathogenesis of the disease