PMID: 

Mol Med Rep. 2019 Aug ;20(2):1808-1818. Epub 2019 Jun 18. PMID: 31257529

Abstract Title: 

Benzyl isothiocyanate suppresses development and metastasis of murine mammary carcinoma by regulating the Wnt/β‑catenin pathway.

Abstract: 

Benzyl isothiocyanate (BITC) has been reported to exhibit antitumor properties in various cancer types; however, the underlying mechanisms of its action remain unclear. In the present study, the efficacy of BITC on murine mammary carcinoma cells was evaluated in vitro and in vivo, revealing a potential mechanism for its action. In vivo bioluminescence imaging indicated dynamic inhibition of murine mammary carcinoma cell growth and metastasis by BITC. A terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay demonstrated that BITC also induced apoptosis. BITC further exhibited antitumorigenic activity in 4T1‑Luc cells in vitro via the inhibition of cell proliferation, induction of apoptosis and cell cycle arrest, and inhibition of cell migration and invasion. Furthermore, the activity of key molecules of the adenomatous polyposis coli (APC)/β‑catenin complex was altered following treatment with BITC, which suggested a potential role for the APC/β‑catenin complex in the BITC‑mediated induction of apoptosis and inhibition of metastasis in murine mammary carcinoma. BITC upregulated the activity of glycogen synthase kinase‑3β and APC proteins, whereas it downregulated β‑catenin expression. The inhibition of metastasis was accompanied with the downregulation of vimentin and upregulation of E‑cadherin. Conversely, BITC did not exhibit toxicity or side effects in the normal mammary epithelial cell lineMCF‑10A. The present study indicated that BITC exhibited anticancer properties due to the induction of breast cancer cell apoptosis and inhibition of breast cancer cell metastasis mediated by the Wnt/β‑catenin signaling pathway.

read more

PMID: 

J Med Food. 2019 May ;22(5):444-450. PMID: 31084542

Abstract Title: 

Sulforaphane Decrease of SERTAD1 Expression Triggers G1/S Arrest in Breast Cancer Cells.

Abstract: 

Studies have identified the potential of chemopreventive effects of sulforaphane (SFN); however, the underlying mechanisms of its effect on breast cancer require further elucidation. This study investigated the anticancer effects of SFN that specifically induces G1/S arrest in breast ductal carcinoma (ZR-75-1) cells. The proliferation of the cancer cells after treatment with SFN was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA content and cell cycle status were analyzed through flow cytometry. Our results demonstrated the inhibition of growth in ZR-75-1 cells upon SFN exposure. In addition, SERTAD1 (SEI-1) caused the accumulation of SFN-treated G1/S-phase cells. The downregulation of SEI-1, cyclin D2, and histone deacetylase 3 suggested that in addition to the identified effects of SFN against breast cancer prevention, it may also exert antitumor activities in established breast cancer cells. In conclusion, SFN can inhibit growth of and induce cell cycle arrest in cancer cells, suggesting its potential role as an anticancer agent.

read more

PMID: 

Mol Med Rep. 2019 Jun ;19(6):4890-4896. Epub 2019 Apr 10. PMID: 31059012

Abstract Title: 

Sulforaphane prevents PC12 cells from oxidative damage via the Nrf2 pathway.

Abstract: 

: The aim of this study was to investigate the protective effect of sulforaphane (SFN) on 1‑methyl‑4‑phenyl pyridine ion (MPP+)‑induced cytotoxicity and to investigate its possible mechanisms.METHODS: PC12 cell toxicity induced by MPP+ served as a cell model of Parkinson's diseases. The cell culture + experiments were divided into four groups based on the different treatments, namely, vehicle control, SFN, MPP+ and SFN pretreatment plus MPP+. Cell viability and apoptosis were examined by MTT assay and flow cytometry, respectively. Expressions of nuclear factor erythroid 2‑related factor 2(Nrf2), heme oxygenase 1 (HO‑1) and nicotinamide quinone oxidoreductase 1 (NQO1) were detected using western blotting.RESULTS: MPP+ reduced the survival rate of PC12 cells in a dose‑ and time‑dependent manner. After 24‑h treatment with 500 µmol/l MPP+, the survival rate of PC12 cells decreased to 58.2±0.03% of that in the control groups. Under the same conditions MPP+ resulted in significant apoptosis of PC12 cells (apoptosis rate: 30.4±0.6%). However, SFN pretreatment significantly attenuated the cell damage induced by MPP+. Furthermore, it was demonstrated that SFN reversed the reduction of Nrf2, HO‑1 and NQO1 expression induced by MPP+.CONCLUSION: SFN may protect PC12 cells from MPP+‑induced damage via activating the Nrf2‑ARE (antioxidant responsive element) pathway.

read more

PMID: 

Mol Ther Oncolytics. 2019 Sep 27 ;14:74-81. Epub 2019 Apr 6. PMID: 31044154

Abstract Title: 

Sulforaphane Induces miR135b-5p and Its Target Gene, RASAL2, thereby Inhibiting the Progression of Pancreatic Cancer.

Abstract: 

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal tumors, with poor therapeutic options in the advanced state. The broccoli-derived anti-inflammatory agent sulforaphane was shown to inhibit the progression of pancreatic cancer and other tumor entities. We examined the involvement of pancreatic cancer cell lines were evaluated by microRNA and gene expression arrays, bioinformatics,analysis, qRT-PCR, western blotting, immunohistochemistry,hybridization, self-renewal and differentiation assays, andxenograft studies. We selected the top nine differentially expressed microRNAs, and miR135b-5p was chosen as the most important candidate for the sulforaphane-induced upregulation of the tumor suppressor gene RASAL2. The expression of miR135b-5p and RASAL2 was almost absent in malignant pancreatic tissues and cell linesbut not in their normal counterparts. Lipofection of miR135b-5p enhanced RASAL2 expression and inhibited ERK1/2 signaling, viability, self-renewal capacityand tumor growth. These results indicate that miR135b-5p acts as a tumor suppressor via the induction of RASAL2 in PDA.

read more

PMID: 

Environ Sci Pollut Res Int. 2019 Aug 7. Epub 2019 Aug 7. PMID: 31392607

Abstract Title: 

The radioprotective effect of N-acetylcysteine against x-radiation-induced renal injury in rats.

Abstract: 

The purpose of this study was therefore to investigate the effects of radiotherapy on the kidney and the potential use of agents such as N-acetylcysteine (NAC) in developing a future therapeutic protocol for radiation-induced nephrotoxicity at the histopathological and biochemical levels. Our study consisted of three groups: control (oral saline solution only; group 1), irradiation (IR; group 2), and NAC + IR (group 3). The irradiation groups received a single dose of whole-body 6-Gy x-irradiation. The NAC group received 300 mg/kg by the oral route for 7 days, from 5 days before irradiation to 2 days after. All subjects were sacrificed under anesthesia 2 days after irradiation. IR increased tubular necrosis scores (TNS), MDA, and caspase-3 expression, while reducing renal tissue GSH levels. We also observed dilation in renal corpuscles and tubules. Capillary congestion was present in the intertubular spaces. NAC reduced the levels of TNS, MDA, and caspase-3 expression, but increased the levels of renal tissue GSH. ROS-scavenging antioxidants may represent a promising means of preventing renal injury in patients undergoing radiotherapy.

read more

PMID: 

Occup Environ Med. 2009 Feb ;66(2):118-23. Epub 2008 Nov 18. PMID: 19017702

Abstract Title: 

Mobile phone base stations and adverse health effects: phase 1 of a population-based, cross-sectional study in Germany.

Abstract: 

OBJECTIVE: The aim of this first phase of a cross-sectional study from Germany was to investigate whether proximity of residence to mobile phone base stations as well as risk perception is associated with health complaints.METHODS: The researchers conducted a population-based, multi-phase, cross-sectional study within the context of a large panel survey regularly carried out by a private research institute in Germany. In the initial phase, reported on in this paper, 30,047 persons from a total of 51,444 who took part in the nationwide survey also answered questions on how mobile phone base stations affected their health. A list of 38 health complaints was used. A multiple linear regression model was used to identify predictors of health complaints including proximity of residence to mobile phone base stations and risk perception.RESULTS: Of the 30,047 participants (response rate 58.6%), 18.7% of participants were concerned about adverse health effects of mobile phone base stations, while an additional 10.3% attributed their personal adverse health effects to the exposure from them. Participants who were concerned about or attributed adverse health effects to mobile phone base stations and those living in the vicinity of a mobile phone base station (500 m) reported slightly more health complaints than others.CONCLUSIONS: A substantial proportion of the German population is concerned about adverse health effects caused by exposure from mobile phone base stations. The observed slightly higher prevalence of health complaints near base stations can not however be fully explained by attributions or concerns.

read more

PMID: 

J Matern Fetal Neonatal Med. 2019 Feb ;32(4):695-699. Epub 2017 Oct 23. PMID: 28988507

Abstract Title: 

Electromagnetic fields in neonatal incubators: the reasons for an alert.

Abstract: 

BACKGROUND: Neonatal incubators are important tools for sick newborns in the first few days of life. Nevertheless, their electric engine, often very close to the newborn's body, emits electromagnetic fields (EMF) to which newborns are exposed. Aim of this paper is to review the available literature on EMF exposure in incubators, and the effects of such exposures on newborns that have been investigated.METHODS: We carried out a systematic review of studies about EMF emissions produced by incubators, using Medline and Embase databases from 1993 to 2017.RESULTS: We retrieved 15 papers that described the EMF exposure in incubators and their biological effects on babies. EMF levels in incubators appear to be between 2 and 100 mG, depending on the distance of the mattress from the electric engine. In some cases, they exceed this range. These values interfere with melatonin production or with vagal tone. Even caregivers are exposed to high EMF, above 200 mG, when working at close contact with the incubators.CONCLUSION: EMF have been described as potentially hazardous for human health, and values reported in this review are an alert to prevent babies' and caregivers' exposure when close to the incubators. A precautionary approach should be adopted in future incubator design, to prevent high exposures of newborns in incubators and of caregivers as well.

read more

PMID: 

Pathophysiology. 2009 Aug ;16(2-3):71-8. Epub 2009 Mar 5. PMID: 19268550

Abstract Title: 

Electromagnetic fields stress living cells.

Abstract: 

Electromagnetic fields (EMF), in both ELF (extremely low frequency) and radio frequency (RF) ranges, activate the cellular stress response, a protective mechanism that induces the expression of stress response genes, e.g., HSP70, and increased levels of stress proteins, e.g., hsp70. The 20 different stress protein families are evolutionarily conserved and act as 'chaperones' in the cell when they 'help' repair and refold damaged proteins and transport them across cell membranes. Induction of the stress response involves activation of DNA, and despite the large difference in energy between ELF and RF, the same cellular pathways respond in both frequency ranges. Specific DNA sequences on the promoter of the HSP70 stress gene are responsive to EMF, and studies with model biochemical systems suggest that EMF could interact directly with electrons in DNA. While low energy EMF interacts with DNA to induce the stress response, increasing EMF energy in the RF range can lead to breaks in DNA strands. It is clear that in order to protect living cells, EMF safety limits must be changed from the current thermal standard, based on energy, to one based on biological responses that occur long before the threshold for thermal changes.

read more

PMID: 

Pathophysiology. 2009 Aug ;16(2-3):149-56. Epub 2009 Mar 10. PMID: 19278839

Abstract Title: 

Long-term exposure to magnetic fields and the risks of Alzheimer's disease and breast cancer: Further biological research.

Abstract: 

OBJECTIVE: Extremely low frequency (ELF) and radio frequency (RF) magnetic fields (MFs) pervade our environment. Whether or not these magnetic fields are associated with increased risk of serious diseases, e.g., cancers and Alzheimer's disease, is thus important when developing a rational public policy. The Bioinitiative Report was an effort by internationally recognized scientists who have spent significant time investigating the biological consequences of exposures to these magnetic fields to address this question. Our objective was to provide an unbiased review of the current knowledge and to provide our general and specific conclusions.RESULTS: The evidence indicates that long-term significant occupational exposure to ELF MF may certainly increase the risk of both Alzheimer's disease and breast cancer. There is now evidence that two relevant biological processes (increased production of amyloid beta and decreased production of melatonin) are influenced by high long-term ELF MF exposure that may lead to Alzheimer's disease. There is further evidence that one of these biological processes (decreased melatonin production) may also lead to breast cancer. Finally, there is evidence that exposures to RF MF and ELF MF have similar biological consequences.CONCLUSION: It is important to mitigate ELF and RF MF exposures through equipment design changes and environmental placement of electrical equipment, e.g., AC/DC transformers. Further research related to these proposed and other biological processes is required.

read more

PMID: 

Naunyn Schmiedebergs Arch Pharmacol. 2019 Jun 14. Epub 2019 Jun 14. PMID: 31197431

Abstract Title: 

Piceatannol protects against cisplatin nephrotoxicity via activation of Nrf2/HO-1 pathway and hindering NF-κB inflammatory cascade.

Abstract: 

This study investigates the molecular mechanisms of the nephroprotective effect of piceatannol (PIC) against cisplatin-induced nephrotoxicity in rats. PIC (10 mg/kg i.p.) was given for 7 days, starting 2 days before cisplatin single injection (7 mg/kg i.p.). Serum creatinine, blood urea nitrogen (BUN), kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin were used as nephrotoxicity markers. Oxidative stress, inflammatory, and apoptotic markers were determined. In addition, the role of PIC in Nrf2 activation and its subsequent induction of antioxidant enzymes, as well as its potential cross talk with nuclear factor kappa-B, were addressed. PIC reversed cisplatin-induced elevation of nephrotoxicity markers and restored the normal kidney ultrastructure. PIC attenuated cisplatin-induced reduction in Nrf2 expression and the relative mRNA level of antioxidant enzymes: hemeoxygenase-1, cysteine ligase catalytic, and modifier subunits, as well as superoxide dismutase and glutathione-S-transferase activities. Cisplatin pro-inflammatory response was reduced by PIC treatment as evidenced by the suppression of nuclear factor kappa-B activation and the subsequent decreased tissue levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and inducible nitric oxide synthase. PIC suppressed cisplatin-induced apoptosis by decreasing p53 and cytochrome C expression and caspase-3 activity. Therefore, PIC may protect against cisplatin-induced nephrotoxicity by modulating Nrf2/HO-1 signaling and hindering the inflammatory and apoptotic pathways.

read more