PMID: 

Front Pharmacol. 2018 ;9:1268. Epub 2018 Nov 21. PMID: 30524274

Abstract Title: 

Nephroprotective Effects of Benzyl Isothiocyanate and Resveratrol Against Cisplatin-Induced Oxidative Stress and Inflammation.

Abstract: 

This study was performed to compare the nephroprotective effects of benzyl isothiocyanate (BITC) and resveratrol (RES) and investigate the nephroprotective efficacy of their combination against cisplatin-induced acute renal injury. Five animal groups (each of eight) received either normal saline, a single intraperitoneal injection of cisplatin (20 mg/kg) at the sixth day, cisplatin plus oral RES (30 mg/kg) or BITC (100 mg/kg in diet), or a combination of both for 10 days. Compared to saline-treated mice, cisplatin-intoxicated mice had significantly higher (

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PMID: 

Cancer Prev Res (Phila). 2019 Mar ;12(3):125-134. Epub 2019 Feb 5. PMID: 30723175

Abstract Title: 

Role of Krüppel-like Factor 4-p21Axis in Breast Cancer Stem-like Cell Inhibition by Benzyl Isothiocyanate.

Abstract: 

Cancer chemoprevention by benzyl isothiocyanate (BITC), which is derived from cruciferous vegetables like garden cress, in a transgenic mouse model of breast cancer is associated with inhibition of breast cancer stem-like cells (bCSC), but the molecular regulators of this effect remain elusive. This study demonstrates a protective effect of Krüppel-like factor 4 (KLF4)-p21axis in bCSC inhibition by BITC. Exposure of human breast cancer cells (MCF-7, MDA-MB-231, and SUM159) to plasma-achievable concentrations of BITC resulted in a robust induction ofmRNA and its protein expression as determined by qRT-PCR and Western blotting or confocal microscopy. BITC-mediated suppression of bCSC markers, including aldehyde dehydrogenase 1 activity and mammosphere frequency, was significantly augmented by transient or stable knockdown of KLF4. Western blotting and IHC revealed relatively higher levels of KLF4 protein in mammary tumor sections from BITC-treated mice in comparison with controls, but the difference was insignificant. Analysis of the breast cancer RNA-Seq data from The Cancer Genome Atlas indicated significant positive correlation between expression ofand that of() but not(). Knockdown of p21protein also amplified BITC-mediated suppression of bCSC. Finally, KLF4 was recruited to the promoter ofas indicated by chromatin immunoprecipitation assay. These results indicate that induction of KLF4-p21axis attenuates inhibitory effect of BITC on bCSC self-renewal. Translational implication of these findings is that breast cancer chemoprevention by BITC may be augmented with a combination regimen involving BITC and an inhibitor of KLF4.

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PMID: 

J Ethnopharmacol. 2019 Oct 5 ;242:112039. Epub 2019 Jun 26. PMID: 31252093

Abstract Title: 

Antihypertensive activity of Petroselinum crispum through inhibition of vascular calcium channels in rats.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Parsley (Petroselinum crispum; P. crispum) is among the popular aromatic vegetables and a part of the daily diet in the Mediterranean area. This plant is widely used in alternative medicine as a remedy against hypertension.THE AIM OF THE STUDY: The aim of the study was to evaluate the antihypertensive activity of the aqueous extract of this plant.MATERIAL AND METHODS: In the current study, the aqueous extract of the aerial parts of parsley (AEPC) was prepared and its antihypertensive activity was evaluated using in vivo and in vitro studies. In the in vivo investigation, anesthetized L-NAME-hypertensive and normotensive rats received orally AEPC (160 mg/kg) during 6 h for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were recorded using a tail cuff and a computer-assisted monitoring device. Concerning the in vitro investigation, isolatedthoracic aortic rings were suspended in a tissue bath and the tension changes were recorded to a data acquisition system.RESULTS: The results indicated that AEPC extract decreased the systolic, diastolic, mean arterial blood pressure in normotensive and hypertensive rats. The data revealed that parsley extract exerts its hypotensive effects through vasodilatory properties via an endothelium-independent pathway. More interestingly, the study demonstrated here that the vasorelaxing ability of AEPC is exerted through both Voltage Operated and Receptor Operated Calcium Channels (VOCC and ROCC).CONCLUSION: The study illustrates the beneficial action of P. crispum as an antihypertensive agent.

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PMID: 

Cancer. 2008 Oct 1 ;113(7 Suppl):1953-68. PMID: 18798534

Abstract Title: 

Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium.

Abstract: 

Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the group's consensus on the current state of scientific findings, and they present a consensus on research priorities to identify which important areas the science should move to address.

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PMID: 

Saudi J Biol Sci. 2019 Jul ;26(5):1089-1092. Epub 2018 May 3. PMID: 31303845

Abstract Title: 

Chemical composition and antimicrobial, antioxidant, and anti-inflammatory activities ofseed oil.

Abstract: 

(garden cress) seed oil was examined for its antimicrobial, antioxidant, and anti-inflammatory activities. The oil was obtained by hydrodistillation, where gas chromatography coupled with mass spectrometry that utilized to study its chemical composition. Microdilution method was used to test the antimicrobial effect of oil against,,,,,, and. The antioxidant activity was assessed by radical scavenging activity assay using 2,2-diphenyl-1-picrylhydrazyl radical. The major constituents found in the oil were 7,10-hexadecadienoic acid, 11-octadecenoic acid, 7,10,13-hexadecatrienoic acid, and behenic acid. The minimum inhibitory concentration (MIC) against all pathogens was 47.5 mg/ml, except for, which showed MIC of 90 mg/ml. The oil demonstrated antioxidant activity in a dose dependent pattern, with a half maximal inhibitory concentration (IC) value of 40 mg/ml, and exerted anti-inflammatory activity, wherein 21% protection was shown at a concentration of 300 μg/ml. Thus,seed oil shows antimicrobial, antioxidant, and anti-inflammatory properties.

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PMID: 

J Integr Med. 2019 May ;17(3):221-228. Epub 2019 Mar 23. PMID: 30940420

Abstract Title: 

Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.).

Abstract: 

OBJECTIVE: Garden cress (Lepidium sativum L.) is an important herb in traditional medicine used to improve production of breast milk in women and semen in men. In the present research the authors evaluated its ability to destroy leukemic cancer (Jurkat E6-1) cells, using the alkaloid extract of this plant.METHODS: Constituents of the alkaloid extract were analyzed by gas chromatography-mass spectrometry (GC-MS) and their cytotoxicity in leukemic cancer cells and healthy peripheral blood mononuclear cells (PBMCs) was assessed. Cell death via apoptosis was confirmed by DNA laddering, caspase-3 activity, annexin V-fluorescein isothiocyanate and mitochondrial toxicity assays. The specific course of gene activation in treated cells was determined through quantitative polymerase chain reaction (qPCR).RESULTS: GC-MS analysis identified six alkaloids and proto-alkaloids, namely, benzyl isothiocyanate (1), 2-ethoxy-4H-3,1-benzoxazin-4-one (2), (4R)-2-(2-aminophenyl)-4-phenyloxazoline (3), 5-acetyl-1,2-dihydro-6-methyl-2-oxo-4-phenyl-3-pyridinecarbonitrile (4), benzo[b][1,8]-naphthyridin-5(10H)-one,2,4,7-trimethyl (5) and 1,4-diaminoanthraquinone (6), in the alkaloid extract of L. sativum. Of these, compound 1 was previously identified in the seeds of L. sativum. Exposure to the alkaloid extract caused death of Jurkat E6-1 cells, with median lethal concentration (LC) of 75.25 µg/mL. However, the alkaloid extract also showed a nontoxic and proliferative (1.6-fold) effect in healthy PBMCs. Further experiments performed with Jurkat cells at LCand sub-LCdoses demonstrated DNA fragmentation, activation of caspase-3 and time-dependant phosphatidylserine translocation (apoptosis) from inner to outer cell membranes. Cell toxicity and assessment of adenosine triphosphate level, together with using qPCR to evaluate expression profile of major apoptosis genes, revealed that apoptosis may be induced by disruption in the mitochondrial outer membrane potential, through activation of extrinsic and intrinsic apoptosis pathways in Jurkat cells.CONCLUSION: The ability of the alkaloid extract of L. sativum seeds to induce apoptosis indicates a potential pharmacological use in cancer chemotherapy. The separation of individual active compounds and further in-depth exploration of the molecular mechanism of apoptosis may lead to novel chemotherapeutic compounds in our future antineoplastic research.

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PMID: 

Int J Oncol. 2019 Jun ;54(6):2106-2116. Epub 2019 Mar 26. PMID: 30942430

Abstract Title: 

Benzyl isothiocyanate suppresses IGF1R, FGFR3 and mTOR expression by upregulation of miR-99a-5p in human bladder cancer cells.

Abstract: 

Benzyl isothiocyanate (BITC) is known for its pharmacological properties against malignant neoplasm, including bladder cancer (BC). The current study investigated microRNAs (miRNA or miR) expression profiles with an emphasis on the role of miR‑99a‑5p in BITC‑treated BC cells. A quantitative polymerase chain reaction (qPCR) microarray containing 79 aberrantly expressed miRNAs in BC was used to detect miRNA expression in BITC‑treated cells. Several dysregulated miRNAs were identified and further confirmed using miRNA stem‑loop reverse transcription (RT)‑qPCR in 5637 cells. Insulin‑like growth factor 1 receptor (IGF1R), fibroblast growth factor receptor 3 (FGFR3) and mammalian target of rapamycin (mTOR) expression were determined by RT‑qPCR and western blotting. Cell viability was evaluated using WST‑1 reagent and apoptosis was monitored by determining the levels of cleaved‑poly ADP‑ribose polymerase and cleaved‑caspase‑3. BITC treatment significantly upregulated miR‑99a‑5p levels in a dose‑dependent manner. miR‑99a‑5p overexpression decreased IGF1R, mTOR and FGFR3 expression, predicted targets of miR‑99a‑5p. In addition, antisense miR‑99a‑5p sequences inhibited BITC‑induced miR‑99a‑5p overexpression, resulting in the restoration of protein expression and decreased cell viability. The current study identified multiple miRNAs responsive to BITC treatment, including miR‑99a‑5p. In addition, the induction of miR‑99a‑5p decreased IGF1R, mTOR and FGFR3 expression in BITC‑treated BC cells. The current study provided novel insight into the antitumor mechanism by which BITC restores miR‑99a‑5p expression and decreases cancer cell survival.

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PMID: 

Braz J Med Biol Res. 2019 Apr 8 ;52(4):e8409. Epub 2019 Apr 8. PMID: 30970087

Abstract Title: 

Benzyl isothiocyanate inhibits invasion and induces apoptosis via reducing S100A4 expression and increases PUMA expression in oral squamous cell carcinoma cells.

Abstract: 

Benzyl isothiocyanate (BITC) has been shown to inhibit invasion and induce apoptosis of various types of cancer. However, its role on human oral squamous cell carcinoma (OSCC) cells is still not well elucidated. In the present study, we investigated the effect of BITC on apoptosis and invasion of SCC9 cells, and its underlying mechanisms in vitro and in vivo. SCC9 cells were exposed to BITC (5 and 25μM) for 24 and 48 h. Cell growth, apoptosis, invasion, and migration were detected in vitro by MTT, FITC-conjugated annexin V/propidium iodide staining followed by flow cytometry, Matrigel-coated semi-permeable modified Boyden, and wound-healing assay. S100A4, PUMA, and MMP-9 expressions were detected to investigate its mechanisms. Xenotransplantation experiments were used to investigate the role of BITC on tumor growth and lung metastasis. BITC inhibited cell viability and induced cell apoptosis in a dose- and time-dependent manner through upregulation of PUMA signals. BITC inhibited cell invasion and migration by downregulation of S100A4 dependent MMP-9 signals. The ip administration of BITC reduced tumor growth but not lung metastasis of SCC9 cells subcutaneously implanted in nude mice. BITC treatment activated pro-apoptotic PUMA and inhibited S100A4-dependent MMP-9 signals, resulting in the inhibition of cell growth and invasion in cultured and xenografted SCC9 cells. Thereby, BITC is a potential therapeutic approach for OSCC.

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PMID: 

Sci Rep. 2019 Jun 20 ;9(1):8866. Epub 2019 Jun 20. PMID: 31222108

Abstract Title: 

Yeast screening system reveals the inhibitory mechanism of cancer cell proliferation by benzyl isothiocyanate through down-regulation of Mis12.

Abstract: 

Benzyl isothiocyanate (BITC) is a naturally-occurring isothiocyanate derived from cruciferous vegetables. BITC has been reported to inhibit the proliferation of various cancer cells, which is believed to be important for the inhibition of tumorigenesis. However, the detailed mechanisms of action remain unclear. In this study, we employed a budding yeast Saccharomyces cerevisiae as a model organism for screening. Twelve genes including MTW1 were identified as the overexpression suppressors for the antiproliferative effect of BITC using the genome-wide multi-copy plasmid collection for S. cerevisiae. Overexpression of the kinetochore protein Mtw1 counteracts the antiproliferative effect of BITC in yeast. The inhibitory effect of BITC on the proliferation of human colon cancer HCT-116 cells was consistently suppressed by the overexpression of Mis12, a human orthologue of Mtw1, and enhanced by the knockdown of Mis12. We also found that BITC increased the phosphorylated and ubiquitinated Mis12 level with consequent reduction of Mis12, suggesting that BITC degrades Mis12 through an ubiquitin-proteasome system. Furthermore, cell cycle analysis showed that the change in the Mis12 level affected the cell cycle distribution and the sensitivity to the BITC-induced apoptosis. These results provide evidence that BITC suppresses cell proliferation through the post-transcriptional regulation of the kinetochore protein Mis12.

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PMID: 

J Agric Food Chem. 2019 Jun 26 ;67(25):7136-7146. Epub 2019 Jun 18. PMID: 31240929

Abstract Title: 

Benzyl Isothiocyanate and Phenethyl Isothiocyanate Inhibit Adipogenesis and Hepatosteatosis in Mice with Obesity Induced by a High-Fat Diet.

Abstract: 

Benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) are organosulfur phytochemicals rich in cruciferous vegetables. We investigated the antiobesity and antihepatosteatosis activities of BITC and PEITC and the working mechanisms involved. C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.5 (L) or 1 g/kg (H) BITC or PEITC for 18 weeks. Compared with the HFD group, BITC or PEITC decreased the final body weight of mice in a dose-dependent manner [39.0± 3.1 (HFD), 34.4 ± 3.2 (BITC-L), 32.4 ± 2.8 (BITC-H), 36.2 ± 4.4 (PEITC-L), and 32.8 ± 2.9 (PEITC-H) g, p

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