• Biomolecules & Therapeutics
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• 제23권1호
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• pp.31-38
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• 2015

Histone acetylation plays a critical role in the regulation of transcription by altering the structure of chromatin, and it may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating the gene expression of components of the TRAIL signaling pathway. In this study, we investigated the effects and molecular mechanisms of trichostatin A (TSA), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in Caki human renal carcinoma cells. Our results indicate that nontoxic concentrations of TSA substantially enhance TRAIL-induced apoptosis compared with treatment with either agent alone. Cotreatment with TSA and TRAIL effectively induced cleavage of Bid and loss of mitochondrial membrane potential (MMP), which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase (PARP), contributing toward the sensitization to TRAIL. Combined treatment with TSA and TRAIL significantly reduced the levels of the cellular Fas-associated death domain (FADD)-like interleukin-$1{\beta}$-converting enzyme (FLICE) inhibitory protein (c-FLIP), whereas those of death receptor (DR) 4, DR5, and FADD remained unchanged. The synergistic effect of TAS and TRAIL was perfectly attenuated in c-$FLIP_L$-overexpressing Caki cells. Taken together, the present study demonstrates that down-regulation of c-FLIP contributes to TSA-facilitated TRAIL-induced apoptosis, amplifying the death receptor, as well as mitochondria-mediated apoptotic signaling pathways.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4601-4607
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• 2014

Red rice contains pharmacological substances including phenolics, oryzanol, tocotrienol and tocopherol. Recently, red rice extract has been employed as a source of antioxidants for inhibition of tumor growth. This study was carried out to evaluate the anti-invasion effects of red rice extract fractions on cancer cells. It was found that at $100{\mu}g/ml$ of crude ethanolic extract (CEE), hexane fraction (Hex) and dichloromethane fraction (DCM) could reduce HT1080 and MDA-MB-231 cancer cell invasion. Hex and DCM revealed higher potency levels than CEE, whereas an ethyl acetate fraction (EtOAc) had no effect. Gelatin zymography revealed that Hex decreased the secretion and activity of matrix metalloproteinase-2 and -9 (MMP-2 and-9). In contrast, the DCM fraction exhibited slightly effect on MMPs secretion and had no effect on MMPs activity. Collagenase activity was significantly inhibited by the Hex and DCM fractions. High amounts of ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol were found in the Hex and DCM fractions and demonstrated an anti-invasion property. On the other hand, proanthocyanidin was detected only in the CEE fraction and reduced MDA-MB-231 cells invasion property. These observations suggest that proanthocyanidin, ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol in the red rice fractions might be responsible for the anti invasion activity. The red rice extract may have a potential to serve as a food-derived chemotherapeutic agent for cancer patients.

• BMB Reports
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• 제53권5호
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• pp.266-271
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• 2020

Breast cancer encompasses a major portion of human cancers and must be carefully monitored for appropriate diagnoses and treatments. Among the many types of breast cancers, triple negative breast cancer (TNBC) has the worst prognosis and the least cases reported. To gain a better understanding and a more decisive precursor for TNBC, two major histone modifications, an activating modification H3K4me3 and a repressive modification H3K27me3, were analyzed using data from normal breast cell lines against TNBC cell lines. The combination of these two histone markers on the gene promoter regions showed a great correlation with gene expression. A list of signature genes was defined as active (highly enriched H3K4me3), including NOVA1, NAT8L, and MMP16, and repressive genes (highly enriched H3K27me3), IRX2 and ADRB2, according to the distribution of these histone modifications on the promoter regions. To further enhance the investigation, potential candidates were also compared with other types of breast cancer to identify signs specific to TNBC. RNA-seq data was implemented to confirm and verify gene regulation governed by the histone modifications. Combinations of the biomarkers based on H3K4me3 and H3K27me3 showed the diagnostic value AUC 93.28% with P-value of 1.16e-226. The results of this study suggest that histone modification analysis of opposing histone modifications may be valuable toward developing biomarkers and targets for TNBC.

• 한국축산식품학회지
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• 제35권4호
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• pp.507-514
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• 2015

Deer velvet antler (DVA) is one of the most popular medicines in China. Numerous studies have demonstrated that velvet antler possess biological effects. However, data regarding its anti-migration activity on prostate cancer is scarce. In this study, we investigated the inhibitory effect of top DVA (T-DVA) on the expression of prostate-specific antigen (PSA) and migration-related genes in the human prostate cancer cell, LNCaP. The T-DVA down-regulated the expression of PSA. In addition, the Radius^TM assay revealed that T-DVA inhibited the migration behavior of prostate cancer cells. Furthermore, the expression of matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) was also decreased with T-DVA. On the contrary, T-DVA increased the tissue inhibition of metallo-proteinase (TIMP)-1 and (TIMP)-2. Taken together, our findings indicate that the T-DVA possesses anti-migration activity on prostate cancer cells. This is the first study of DVA to report the anti-migration activity on prostate cancer.

• 대한한의학방제학회지
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• 제26권3호
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• pp.251-259
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• 2018

Objective : Kurarinone is one of the flavonoids isolated from Sophorae Radix with various biological activities including anti-microbial effect. In this study, we investigated the effects of Kurarinone on tert-butyl hydroperoxide (tBHP)-induced oxidative stress finally leading to apoptosis in human hepatoma cell line HepG2. Methods : To determine the effects on cell viability, the cells were exposed to tBHP ($100{\mu}mol/l$) after pretreatment with kurarinone (0.5 and $1{\mu}g/ml$). Cell viability was measured by MTT assay. To reveal the possible mechanism of cytoprotectivity of kurarinone, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, and expression of caspase were examined. Results : tBHP-induced cell death was due to oxidative stress and the resulting apoptosis. Kurarinone dose-dependently protected cells from apoptosis when determined by MTT and TUNEL assay. Consistent with this observation, decreased expression of pro-caspase 3/9 protein by tBHP was restored by kurarinone. Kurarinone also showed anti-oxidative effects by inhibiting generation of ROS and depletion of GSH in tBHP-stimulated HepG2 cells. In addition, kurarinone significantly recovered disruption of mitochondrial membrane potential (MMP) as a start sign of hepatic apoptosis induced by oxidative stress. Conclusion : From these results, it was concluded that kurarinone protected tBHP-induced hepatotoxicity with anti-oxidative and anti-apoptotic activities. Our results suggest that kurarinone might be beneficial to hepatic disorders caused by oxidative stress.

• 생명과학회지
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• 제16권3호
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• pp.442-446
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• 2006

참죽나무는 멀구슬과 나무로서 한국과 중국에 널리 분포하고 있다. 한방에서는 장염(腸炎), 이질(痢疾), 개선(疥癬) 등의 치료에 이용되고 있다. 본 연구는 참죽나무 잎에서 3종의 flavonol glycosides를 분리하여 NMR을 통해 구조를 확인한 결과, kaempferol-3-O-rhamnoside (1), quercetin-3-O-rhamnoside (2)와 quercetin-3-O-glucoside(3)로 구조 동정되었다. 분리된 화합물들의 생리활성은 matrix metalloproteinase-2 저해 활성과 인체암 세포주에 대한 세포독성과 apoptosis실험을 통하여 항암효과를 조사하였다. 그 결과 인체암 세포주에 대한 세포독성과 apoptosis 저해활성은 나타내지 않았으나, MMP-2활성저해 조사에서는 강한 저해 효과를 나타내었다. 특히 quercetin-3-O-glucoside는 암세포에 직접적인 독성을 보이는 것이 아니라 암의 침윤과 전이에 특이적으로 작용하는 물질로 보여진다.

• 생명과학회지
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• 제24권5호
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• pp.573-587
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• 2014

혈관신생은 모든 조직의 성장과 발달, 그리고 상처회복 등에 매우 중요하다. 지방조직은 우리 몸에서 가장 혈관이 발달된 조직으로서 각 지방세포들은 모세혈관에 둘러싸여 있으며 신생혈관들은 지방세포에 영양분과 산소를 공급한다. 혈관의 내피세포들은 파라크린 신호경로, 세포외 성분, 세포들 간의 직접적인 작용을 통해 지방세포와 교류한다. 활성화된 지방세포들은 VEGF, FGF-2, leptin, HGF와 같은 혈관신생인자들을 생성하며, 이들은 단독으로 혹은 협력하여 혈관신생을 증가시키고 지방조직의 성장과 대사를 촉진한다. 따라서 혈관신생 억제제들은 비만과 비만관련 질환을 치료하는데 유용할 것으로 생각된다.

• 한국수정란이식학회지
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• 제33권3호
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• pp.107-117
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• 2018

The purpose of this study is to expression pattern of melanogenesis associate genes on cultured melanocyte layer cells in Korean Brindle Cattle(Dark, Brindle and Yellow) were analyzed to evaluate the effects of sex hormones on the control of melanogenesis pathways. Korean Brindle Cattle(Dark, Brindle and Yellow) melanocyte in the skin cells was collected. after the addition of estrogen and testosterone, the culture was analyzed for expression of cell activity and melanin genes for 72 hours. For the analysis of estrogen in different coat color other than the melanogenesis-related genes it is increasingly yellow showed low expression. in particular, the cells of the brindle coat color is low active and expression of genes. However, the testosterone was low, the expression of cell activity inhibiting MMP-2. the expression of melanin genes actually showed a tendency to increase gradually, which is testosterone compared with the estrogen to be considered that affect the skin cell layer brindle coat color. In this study, stimulation with estrogen triggered the inhibition of MC1R of the melanocyte in brindle coat color, but testosterone is induced MC1R in melanocyte. Therefore, considered the eumelanin or phaeomelanin activation are controlled caused by differential expression of sex hormones on melanocyte in Korean Brindle Cattle.

• Nutrition Research and Practice
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• 제8권5호
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• pp.487-493
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• 2014

BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-${\kappa}B$, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.