• 생명과학회지
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• 제16권3호
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• pp.369-374
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• 2006

본 연구는 단삼 분획추출물로부터 in vitro와 in vivo상에서 QR과 GST의 활성 유도와 GSH의 함량변화를 지표로 암예방 효과를 측정하였다. Hepalcla7 세포에 대한 in vitro상에서의 실험결과 QR 활성 유도율은 70% EtOH 추출물 50 ${\mu}g/ml$ 처리군에서 2.5배로 가장 높은 유도율을 나타내었고, GST 활성 측정은 EtOAc추출물 50 ${\mu}g/ml$농도에서 1.4배의 유도율을 나타내었다. GSH 생성변화를 살펴본 결과에서는 $H_2O$추출물, 70% EtOH 추출물 그리고 water layer 추출물 50 ${\mu}g/ml$ 농도에서 높은 생성율을 나타내었다. 이상의 결과에서 QR활성과 GSH 함량변화에서 높은 증가효과를 나타낸 70% EtOH 추출물을 관류법으로 마우스에 투여하여 in vivo 상에서의 QR과 GST의 활성 변화와 GSH 함량을 측정한 결과 QR, GST활성과 GSH함량이 250 mg 투여시 각각 1.7배 및 1.5배의 활성 증가와 1.4배 함량증가를 측정할 수 있었음으로 70% EtOH추출물은 암예방효과가 가장 높은 것으로 생각된다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권4호
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• pp.333-344
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• 2008

The objectives of this study was to explore the growth pattern of the oral squamous cell carcinoma when overexpressed COX was inhibited, explore the pathway that COX inhibitors suppressed the proliferation of cancer cells, and then hereafter investigate the potential of COX as chemopreventive target for oral squamous cell carcinoma. For confirming the COX-dependent effect and mechanisms on growth of the oral cancer cells, we treated the nonselective NSAID, Mefenamic acid and COX-2 selective inhibitor, Celecoxib in HN4 cell line. And then the cell line was evaluated with MTT assay and growth curve, the production of PGE2, total RNA extraction and RT-PCR analysis, and TEM The results were obtained as follows: 1. After administration of medication, in the result of MTT assay, Celecoxib inoculated group inhibit the cell growth rather than Mefenamic acid inoculated group. 2. The growth curve of cell line showed as time passes by there was a dramatic cell growth in the control group, and gradual growth inhibition was found in medication inoculated group and, in Celecoxib inoculated group there was more inhibition of cell growth. 3. After the administration of medication, Celecoxib tend to inhibit the synthesis of PGE2 more than Mefenamic acid. Mefenamic acid inhibit the synthesis of PGE2 more as the concentration gets high, but Celecoxib inhibited the synthesis of PGE2 even in low concentration. 4. After the administration of medication, the revelation of COX mRNA in cell line, there was a 50% decrease in COX-1, 60% decrease in COX-2 as in $50{\mu}M$ Mefenamic acid, and in Celecoxib $50{\mu}M$ there was not much difference in COX-1 and 90% decrease in COX-2 was found. 5. HN4 cell line showed broken nucleus and tangled cytoskeleton bundles in cytoplasm which meant apoptotic features after the treatment of Celecoxib in TEM view. Depending on the above results, we estimate that the inhibition of the expression of COX-2 cause the growth suppression of the oral squamous cell carcinoma, and it get achieved through pathway of reduced PGE2 production and increased apoptosis. In addition to, because COX-2 selective inhibitor specifically act to COX-2, it is considered that COX-2 selective inhibitor has the adequate potential as chemopreventive agent for oral squamous cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.427-436
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• 2012

Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction.Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product to be developed as not only the source of co-chemotherapeutic agents, but also phyto-estrogens. Therefore, further study needs to be conducted to explore the potential of citrus fruits in overcoming cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2015-2020
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• 2012

Oleanolic acid (OA) is a naturally occurring triterpenoid in food materials and is a component of the leaves and roots of Olea europaea, Viscum album L., Aralia chinensis L. and more than 120 other plant species. There are several reports validating its antitumor activity against different cancer cells apart from its hepatoprotective activity. However, antitumor activity against skin cancer has not beed studied well thus far. Hence the present study of effects of OA against HaCaT (immortalized keratinocyte) cells - a cell-based epithelial model system for toxicity/ethnopharmacology-based studies - was conducted. Radical scavenging activity ($DPPH{\cdot}$) and FRAP were determined spectrophotometrically. Proliferation was assessed by XTT assay at 24, 48 and 72 hrs with exposure to various concentrations (12.5-200 ${\mu}M$) of OA. Apoptotic induction potential of OA was demonstrated using a cellular DNA fragmentation ELISA method. Morphological studies were also carried out to elucidate its antitumor potential. The results revealed that OA induces apoptosis by altering cellular morphology as well as DNA integrity in HaCaT cells in a dose-dependent manner, with comparatively low cytotoxicity. The moderate toxicity observed in HaCaT cells, with induction of apoptosis, possibly suggests greater involvement of programmed-cell death-mediated mechanisms. We conclude that OA has relatively low toxicity and has the potential to induce apoptosis in HaCaT cells and hence provides a substantial and sound scientific basis for further validation studies.

• 동의생리병리학회지
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• 제22권5호
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• pp.1322-1329
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• 2008

Mulberry has been reported to contain wide range of polyphenols and have chemopreventive activity. However, little has been known regarding the effect of mulberry fruits on cell viability in human glioma cells. The present study was undertaken to examine the effect of mulberry fruit (Mar; Fructus) on cell viability and to determine its underlying mechanism in human glioma cells. Cell viability and cell death were estimated by MTT assay and trypanblue exclusion assay, respectively. Reactive oxygen species (ROS) generation was measured using the fluorescence probe DCFH-DA. The mitochondrial transmembrane potential was measured with $DiOC_6$(3). Bax expression and cytochrome c release were measured by Western blot analysis. Caspase activity was estimated using colorimetric kit. Mori Fructus resulted in apoptotic cell death in a dose- and time-dependent manner. Mori Fructus increased ROS generation and the Mori Fructus-induced cell death was also prevented by antioxidants, suggesting that ROS generation plays a critical role in Mari Fructus-induced cell death. Western blot analysis showed that Mori Fructus treatment caused an increase in Bax expression, which was inhibited by the antioxidant N-acetylcysteine (NAC). Mori Fructus induced depolarization of mitochondrial membrane potential and its effect was inhibited by the antioxidants NAC and catalase. Mori Fructus induced cytochrome c release, which was inhibited by NAC. Caspase activity was stimulated by Mori Fructus and caspase inhibitors prevented the Mori Fructus-induced cell death. These findings suggest that Mori Fructus results in human glioma cell death through ROS-dependent mitochondrial pathway in human glioma cells.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4815-4822
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• 2012

Invasion and metastasis are the major causes of cancer-related death. Pharmacological or therapeutic interventions such as chemoprevention of the progression stages of neoplastic development could result in substantial reduction in the incidence of cancer mortality. (-)-Epigallocatechin-3-gallate (EGCG), a promising chemopreventive agent, has attracted extensive interest for cancer therapy utilizing its antioxidant, anti-proliferative and inhibitory effects on angiogenesis and tumor cell invasion. In this study, we assessed the influence of EGCG on the proliferative potential of HeLa cells by cell viability assay and authenticated the results by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Further we analyzed the anti-invasive properties of EGCG by wound migration assay and gene expression of MMP-9 and TIMP-1 in HeLa cells. Our results indicated that EGCG induced growth inhibition of HeLa cells in a dose- and time-dependent manner. It was observed that cell death mediated by EGCG was through apoptosis. Interestingly, EGCG effectively inhibited invasion and migration of HeLa cells and modulated the expression of related genes (MMP-9 and TIMP-1). These results indicate that EGCG may effectively suppress promotion and progression stages of cervical cancer development.

• Journal of Nutrition and Health
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• 제40권2호
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• pp.147-153
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• 2007

In this study, we investigated the anticancer activity of the fin of Thunnus Thynnus (TT). TT was extracted with methanol (TTM), and then further fractionated into four subfractions by using solvent partition method, affording hexane (TTMH), methanol (TTMM), butanol (TTMB) and aquous (TTMA) soluble fractions. We determined the cytotoxicity of these four fractions in four kind of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. The TTMM showed the strongest cytotoxic effect at the concentration of 150 ${\mu}g/mL$, displaying 95% on the HepG2 cell lines and 82% on MCF-7 cell line. The morphological changes such as membrane shirinking and blebbing of cells were also observed by TTMM treatment in HT29 cell. In addition, we observed that quinone reductase (QR) activity was elevated by only TTMM and TTMH treatments in HepG2 cell. QR activity was increased to around 2.0 and 1.8 times in TTMM and TTMH treated HepG2 cell at 100 ${\mu}g/mL$, respectively, compared to that in control. Although further studies are needed, the present work could suggest that the fin of TT has a potential to be usable as a chemopreventive agent against cancer.

• BMB Reports
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• 제42권12호
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• pp.806-811
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• 2009

Recently, various phenolic acid phenethyl ureas (PAPUs) have been synthesized from phenolic acids by Curtius rearrangement for the development of more effective anti-oxidants. In this study, we examined the anti-tumor activity and cellular mechanism of the synthetic compound (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea (PAPU1) using melanoma B16/F10 and M-3 cells. Results showed that PAPU1 inhibited the cell proliferation and viability, but did not induce cytotoxic effects on primary cultured fibroblasts. PAPU1 induced apoptotic cell death rather than necrosis in melanoma cells, a result clearly proven by the shift of cells into sub-$G_1$ phase of the cell cycle and by the substantial increase in cells positively stained with TUNEL or Annexin V. Collectively, this study revealed that PAPU1 induced apoptosis in a caspase-dependent manner, suggesting a potential role as a cancer chemopreventive agent for melanoma cells.

• Journal of Microbiology and Biotechnology
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• 제10권6호
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• pp.851-857
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• 2000

The activities of phase II and antioxidant enzymes in the liver, lung, kidney, stomach, and colon of mice were examined following intragastric application of polysaccharides extracted from soybeans fermented with either Agrocybe Cylindracea (AC) or Phellinus ignarius (PI). The intragastric application of the extracts to mice for 14 days significantly increased the activities of quinone reductase (QP) and glutathione S-transferase (GST) in the liver and kidney, glutathione (GSH) and superoxide dismutase (SOD) in the liver, kidney, lung, and stomach, and glutathione peroxidase (GSH-Px) in the liver, lung, and kidney. In general, the elevation of the phase II and antioxidant enzymes activities was more pronounced in the liver and kidney as compared to the lung, stomach, and colon. Accordingly, these finding suggest that polysaccharides extracted from soybeans fermented with A. cylindracea or P. igniarius have a cancer chemopreventive potential in various target organs.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.113-117
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• 2005

Organosulfur compounds have been shown to exert an anti-cancer activity. In an attempt to develop novel chemopreventive and anti-cancer agents for liver cancer, we synthesized allylthiopyridazine derivatives. We have previously shown that allylthiopyridazine derivatives exert inhibitory effects on proliferation, invasion and migration of SK-Hep-1 hepatocarcinoma cells in vitro. The in vivo anti-tumor effect of 3-methvl-6-allylthiopy-ridazine, named as K6, was also reported. In this study, we further investigated the preclinical anti-cancer efficacy of K6 for hepatocarcinoma using nude mice xenografted with Hep-G2 hepatocellular carcinoma cells. K6(20-100 mg/kg, orally administered everyday for 30 days) markedly decreased the tumor volume of Hep-G2 cell-transplanted nude mice as evidenced by ultrasonographic and plethysmogranhic analyses. The inhibitory effect on tumor volume was lower than that exerted by doxorubicin (2 mg/kg), intravenously injected) which was used as a positive control. This study shows that K6 efficiently suppresses xenograft tumor growth, revealing K6 as apotential anti-cancer agent for suppressing in vivo progression of liver cancer. Given that hepatocarcinoma is among the most prevalent and lethal malignancies and there is no effective treatment to date, our study may contribute to the potential drug development for liver cancer.