• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2607-2610
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• 2013

Malignant glioma, also known as brain cancer, is the most common intracranial tumor, having an extremely high mortality and recurrence rate. The survival rate of the affected patients is very low and treatment is difficult. Hence, growth inhibition of glioma has become a hot topic in the study of brain cancer treatment. Among the various isothiocyanate compounds, it has been confirmed that benzyl isothiocyanate (BITC) can inhibit the growth of a variety of tumors, including leukemia, glioma and lung cancer, both inside and outside the body. This study explored inhibitory effects of BITC on human glioma U87MG cells, as well as potential mechanisms. It was found that BITC could inhibit proliferation, induce apoptosis and arrest cell cycling of U87MG cells. In addition, it inhibited the expression of SOD and GSH, and caused oxidative stress to tumor cells. Therefore, it is believed that BITC can inhibit the growth of U87MG cells outside the body. Its mechanism may be related to the fact that BITC can cause oxidative stress to tumor cells.

• 한국식품과학회지
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• 제31권1호
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• pp.206-211
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• 1999

천연에서 발견되는 휘발성 물질인 isothiocyanate계(ITCs) 물질을 대상으로 Listeria monocytogenes, Bacillus subtilis, Pseudomonas fluorescens, Escherichia coli, Erwinia carotovora, Saccharomyces cerevisiae, Candida albicans, Aspergillus oryzae and Penicillium roqueforti 등 9종의 균주에 대한 증식 억제 효과를 측정하였으며 초산과 혼합하여 사용할 때 상승효과를 비교하였다. Allyl isothiocyanate (AIT), benzyl isothiocyanate (BIT) 및 ethyl isothiocyanate (EIT)가 대상 균주 모두에 $100{\sim}200\;{\mu}g/dish$ 수준의 최소증식저해농도(MIC)를 보였고 증식 저해 정도는 곰팡이>효모>Gram 음성 세균>Gram 양성 세균 순 이었다. 초산은 $50{\sim}500\;{\mu}g/dish$로 ITCs 보다 MIC가 낮았다. ITCs와 초산을 혼합하여 사용하는 경우 대부분의 실험 대상 균주에 대하여 증식 저해 상승효과가 인정되었고 AIT의 경우 AIT 단독 또는 초산 단독으로 사용할 때보다 $2{\sim}10$배 이상 효과가 상승하였으며 전체적으로 증식 억제 경향은 ITCs 단독 사용할 때와 같은 경향이었다.

• Journal of Nutrition and Health
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• 제18권4호
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• pp.293-300
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• 1985

Volatile components of Korean horseradish roots harvested at different dates were prepared by steam distillation. Samples were examined by gas chromatography (GC) and combined gas chromatography-mass spectrometry (GC-MS). The major pungent constituent, allyl isothiocyanate was confirmed add tended to increase with delayed harvest time. Pungent principles also included allyl thiocyanate, 2-phenethyl, 2-butyl, 4- pentenyl, benzyl and 3-methylthiopropyl isothiocyanates. Infrared (IR) spectroscopy study showed that allyl isothiocyanate - thiocyanate interconversion did not occur under the condition of this study.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8225-8228
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• 2014

Glioma is one of the most common tumors in China and chemotherapy is critical for its treatment. Recent studies showed that benzyl isothiocyanate (BITC) could inhibit the growth of glioma cells, but the mechanisms are not fully understood. This study explored the inhibitory effect of BITC on invasion and angiogenesis of U87MG human glioma cells in vitro and in vivo, as well as potential mechanisms. It was found that BITC could inhibit invasion and angiogenesis of human glioma U87MG cells by inducing cell cycle arrest at phase G2/M. It also was demonstrated that BITC decreased expression of cyclin B1, p21, MMP-2/9, VE-cadherin, CD44, CXCR4 and MTH1, the activity of the telomerase and $PKC{\zeta}$ pathway. Microarray analysis was thus useful to explore the potential target genes related to tumorigenic processes. BITC may play important roles in the inhibition of invasion and angiogenesis of human glioma cells.

• Preventive Nutrition and Food Science
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• 제19권4호
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• pp.268-273
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• 2014

The induction of detoxification enzymes by benzyl isothiocyanate (BITC) and its synthetic N-acetyl-L-cysteine (NAC) conjugate (NAC-BITC) was examined in Hepa1c1c7 murine hepatoma cells. BITC and NAC-BITC inhibited Hepa1c1c7 cell growth in a dose-dependent manner. Cell growth was 4.5~57.2% lower in Hepa1c1c7 cells treated with $0.1{\sim}1.0{\mu}M$ BITC than in control-treated Hepa1c1c7 cells. The NAC-BITC treatment had a similar inhibitory pattern on Hepa1c1c7 cell growth; $0.5{\mu}M$ and $10{\mu}M$ NAC-BITC decreased cell growth by 13.6% and 47.4%, respectively. Treatment of Hepa1c1c7 cells with $0.1{\sim}2.0{\mu}M$ BITC also elicited a dose-response effect on the induction of quinone reductase quinone reductase (QR) activity and QR mRNA expression. Treatment with $1{\mu}M$ and $2{\mu}M$ BITC caused 1.8- and 2.8-fold inductions of QR mRNA, respectively. By comparison, treatment with $1{\mu}M$ and $2{\mu}M$ NAC-BITC caused 1.6-and 1.9-fold inductions of QR mRNA, respectively. Cytochrome P450 (CYP) 1A1 and CYP2E1 induction were lower in $0.1{\sim}2{\mu}M$ BITC-treated cells than in control-treated cells. CYP2E1 activity was 1.2-fold greater in $0.1{\mu}M$ NAC-BITC-treated cells than in control-treated cells. However, the CYP2E1 activity of cells treated with higher concentrations (i.e., $1{\sim}2{\mu}M$) of NAC-BITC was similar to the activity of control-treated cells. Considering the potential of isothiocyanatesto prevent cancer, these results provide support for the use of BITC and NAC-BITC conjugates as chemopreventive agents.

• Biomolecules & Therapeutics
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• 제30권4호
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• pp.348-359
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• 2022

Gastric adenocarcinoma is among the top causes of cancer-related death and is one of the most commonly diagnosed carcinomas worldwide. Benzyl isothiocyanate (BITC) has been reported to inhibit the gastric cancer metastasis. In our previous study, BITC induced apoptosis in AGS cells. The purpose of the present study was to investigate the effect of BITC on autophagy mechanism in AGS cells. First, the AGS cells were treated with 5, 10, or 15 μM BITC for 24 h, followed by an analysis of the autophagy mechanism. The expression level of autophagy proteins involved in different steps of autophagy, such as LC3B, p62/SQSTM1, Atg5-Atg12, Beclin1, p-mTOR/mTOR ratio, and class III PI3K was measured in the BITC-treated cells. Lysosomal function was investigated using cathepsin activity and Bafilomycin A1, an autophagy degradation stage inhibitor. Methods including qPCR, western blotting, and immunocytochemistry were employed to detect the protein expression levels. Acridine orange staining and omnicathepsin assay were conducted to analyze the lysosomal function. siRNA transfection was performed to knock down the LC3B gene. BITC reduced the level of autophagy protein such as Beclin 1, class III PI3K, and Atg5-Atg12. BITC also induced lysosomal dysfunction which was shown as reducing cathepsin activity, protein level of cathepsin, and enlargement of acidic vesicle. Overall, the results showed that the BITC-induced AGS cell death mechanism also comprises the inhibition of the cytoprotective autophagy at both initiation and degradation steps.

• Toxicological Research
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• 제18권3호
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• pp.249-257
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• 2002

Cytochrome P450 3As such as 3A4 and 3A5 metabolize a wide range of pharmaceutical compounds. The vectors for the expression of fusion protein containing an N-terminal human P450 3A4 or P450 3A5 sequences and a C-terminal rat NADPH-cytochrome P450 reductase moiety were constructed. These plasmids were used to express the fusion protein in Escherichia coli DH5$\alpha$ cells. High levels of expression were achieved (100~200 nmol/liter) and the expressed fusion protein in E. coli membranes were catalytically active for nifedipine oxidation, a typical enzymatic activity of P450 3A4. The NADPH-P450 reductase activities of these fusion protein were also determined by measuring reduction of cytochrome c. To fine a specific Inhibitor of P450 3A4 from naturally occurring chemicals, a series of isothiocyanate compounds were evaluated for the inhibitory activity of P450 using the fusion proteins in E. coli membranes. Of the five isothiocyanates (phenethyl isothiocyanate, phenyl isothiocyanate, benzol isothiocyanate, benzoyl isothiocyanate and cyclohexyl isothiocyanate) tested, benzoyl isothiocyanate showed a strong inhibition of P450 3A4 with an $IC_{50}$value of 2.8 $\mu\textrm{M}$. Our results indicate that the self-sufficient fusion protein will be very useful tool to study the drug metabolism and benzyl isothiocyanate may be valuable for characterizing the enzymatic properties of P450 3A4.

• 한국식품저장유통학회지
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• 제22권6호
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• pp.886-892
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• 2015

십자화과 채소의 주요 성분인 10종의 isothiocyanates(ITCs)와 무 가수분해물을 대상으로 6개의 넙치 어병세균에 대하여 항균활성을 측정하여 ITCs의 화학적 구조와 항균성과의 관계를 비교하였다. 항균활성은 sulforaphane, sulforaphene, PEITC, erucin, BITC, iberin, I3C가 높았으며, AITC, PITC, HITC는 낮았다. 어병 세균별로 ITCs에 대한 민감성은V. harveyi가 가장 높았으며, 그 다음으로E. tarda, P. damselae, S. parauberis, S. iniae, V. ichthyoenteri 순으로, 그람음성균이 그람양성균에 비하여 민감성이 높았다. 무가수분해물의 최소저해농도(MIC)는 S. iniae에 대해서 0.250 mg/mL(raphasatin의 농도)로 가장 높은 항균활성을 나타내었고, S. parauberis는 0.438 mg/mL, E. tarda와 V. harveyi는 0.500 mg/mL로 높은 항균활성을 나타내었다. ITCs의 화학구조에 따른 어병 세균에 대한 항균활성은 aliphatic ITCs 중에서는 sulforaphene, sulforaphane, erucin, iberin의 항균활성이 높았으며, benzene ring을 함유하고 있는 aromatic ITCs 중에서는 PEITC과 BITC이 가장 항균활성이 높았다. 이중결합이 없는 sulforaphane은 이중결합을 가지고 있는 sulforaphene에 비하여 항균활성이 대부분의 균주에 대해서 높았다. Thiol group을 가지고 있는 erucin은 sulfinyl group을 가지고 있는 sulforaphane에 비하여 일부균주에 대하여 높은 항균활성을 나타내었다. 탄소사슬의 길이가 긴 PEITC는 탄소사슬의 길이가 짧은 BITC에 비하여 4가지 균주에 대하여 항균활성이 높았다. 이상의 결과로 부터 십자화과 유래 ITCs는 넙치 어병 항균제로 활용할 수 있을 것으로 추정되었다.