• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6939-6944
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• 2014

Sulfasalazine (SSZ) is an anti-inflammatory drug that has been used to treat inflammatory bowel disease and rheumatoid arthritis for decades. Recently, some reports have suggested that SSZ also has anti-cancer properties against human tumors. However, little is known about the effects of SSZ on oral cancer. The aim of this study was to investigate the anti-cancer effects of SSZ in oral squamous cell carcinoma (OSCC) cells and to elucidate the mechanisms involved. The authors investigated the anti-proliferative effect of SSZ using the MTT method in HSC-4 cells (an OSCC cell line). Cell cycle analysis, acidic vesicular organelle (AVO) staining, monodansylcadaverine (MDC) staining and Western blotting were also conducted to investigate the cytotoxic mechanism of SSZ. SSZ significantly inhibited the proliferation of HSC-4 cells in a dose-dependent manner. In addition, SSZ induced autophagic cell death, increased microtubule-associated protein 1 light chain (MAP1-LC; also known as LC) 3-II levels, as well as induced punctate AVO and MDC staining, resulted in autophagic cell death. Furthermore, these observations were accompanied by the inhibition of the Akt pathway and the activation of ERK pathway. These results suggest that SSZ promotes autophagic cell death via Akt and ERK pathways and has chemotherapeutic potential for the treatment of oral cancer.

• 한국자원식물학회지
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• 제30권6호
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• pp.640-646
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• 2017

In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

• Journal of Nutrition and Health
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• 제55권2호
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• pp.240-249
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• 2022

본 연구에서는 인간 유방암 세포 라인인 MDA-MB-231 세포에서 GD에 의해 EVs분비 억제에 의한 항암효과를 처음으로 확인하고자 하였다. MDA-MB-231 세포에 GD를 처리하였을 때 농도 의존적으로 세포의 증식률을 억제하는 것을 MTT assay를 통해 확인할 수 있었으며, ROS 염색과 apoptosis marker 단백질인 p-JNK단백질의 증가를 통해 GD에 의한 세포의 증식 억제 효과가 세포사멸에 의한 것임을 유추할 수 있었다. 또한 wound-healing assay, 세포 침윤 및 VEGF 농도를 측정한 결과 GD가 암세포의 이동, 전이 능력을 억제하는 것을 확인하였다. Nanosight를 통해서 MDA-MB-231 세포에서 분비되는 대조군 EVs 및 GD에 의해 변화된 EVs의 사이즈를 확인하였다. 마지막으로 GD를 처리한 MDA-MB-231 세포에서 분비된 EVs보다 GD를 처리하지 않은 대조군에서 분비된 EVs의 단백질 및 particles수가 유의적으로 감소하는 것을 확인을 하였다. 그리고 GD가 MDA-MB-231 세포에서 EVs분비를 감소시키는 것을 대표적인 exosome marker인 TSG101, CD63의 발현 감소로 확인할 수 있었다. 이러한 결과로 인해 GD가 암세포의 EVs 분비를 감소시켜 암세포의 성장 및 전이를 억제하였음을 확인하였다. 본 연구는 GD가 인간 유방암 세포인 MDA-MB-231 세포의 EVs 분비를 억제하는 효과가 있음을 제시하고 있다. 따라서 GD가 유방암의 화학요법 약물로 작용할 수 있음을 시사한다.

• Nutrition Research and Practice
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• 제9권2호
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• pp.111-116
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• 2015

BACKGROUND/OBJECTIVES: Inonotus obliquus (I. obliquus, Chaga mushroom) has long been used as a folk medicine to treat cancer. In the present study, we examined whether or not ethanol extract of I. obliquus (EEIO) inhibits cell cycle progression in HT-29 human colon cancer cells, in addition to its mechanism of action. MATERIALS/METHODS: To examine the effects of Inonotus obliquus on the cell cycle progression and the molecular mechanism in colon cancer cells, HT-29 human colon cancer cells were cultured in the presence of $2.5-10{\mu}g/mL$ of EEIO, and analyzed the cell cycle arrest by flow cytometry and the cell cycle controlling protein expression by Western blotting. RESULTS: Treatment cells with $2.5-10{\mu}g/mL$ of EEIO reduced viable HT-29 cell numbers and DNA synthesis, increased the percentage of cells in $G_1$ phase, decreased protein expression of CDK2, CDK4, and cyclin D1, increased expression of p21, p27, and p53, and inhibited phosphorylation of Rb and E2F1 expression. Among I. obliquus fractions, fraction 2 (fractionated by dichloromethane from EEIO) showed the same effect as EEIO treatment on cell proliferation and cell cycle-related protein levels. CONCLUSIONS: These results demonstrate that fraction 2 is the major fraction that induces $G_1$ arrest and inhibits cell proliferation, suggesting I. obliquus could be used as a natural anti-cancer ingredient in the food and/or pharmaceutical industry.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.21-30
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• 2024

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.

• Journal of Acupuncture Research
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• 제22권6호
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• pp.37-50
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• 2005

Objectives : The purpose of this study was to investigate the anti-caner effect of Bee Venom and Melittin on the prostatic cancer cell(PC-3). The goal of study is to ascertain whether Bee Venom and Melittin inhibits the cell growth and cell cycle of PC-3, or the expression of relative genes and whether the regression of PC-3 cell growth is due to cell death or the expression of gene related to apoptosis. Methods : After the treatment of Pc-3 cells with Bee Venom and Melittin, we performed Fluorescence microscope, MTT assay, Western blotting, Flow cytometry, PAGE electrophoresis and Surface plasmon resonance analysis to identify the cell viability, apoptosis and gene related to apoptosis. Results : 1. Compared with Control cell, the inhibition of cell growth reduced in proportion with the dose of Bee Venom or Melittin($0{\sim}10{\mu}g/ml$) in PC-3. 2. In PC-3, Cell viabilities of Bee Venom or Melittin treatment was decreased significantly. 3. The nucli of Control cells were stained round and homogenous in DAPI staining, but those of PC-3 were stained condense and splitted. 4. In PC-3, apoptosis of Bee Venom or Melittin treatment was increased significantly. 5. Bax, Caspase-3 and P ARP of Bee Venom or Melittin treatment was increased significantly and Bcl-2 of Bee Venom or Melittin treatment was decreased significantly. Caspase-9 of Bee venom treatment was increased significantly. Conclusion : These results indicate that Bee Venom and Melittin inhibits the growth of prostate cancer cells, has anti-cancer effects by inducing apoptosis. We wish that the anti-cancer effects of Bee Venom and Melittin are used to clinical caner treatment.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.487-492
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• 2011

In our previous study, we investigated Chenopodium album Linne (CAL) ethanol extract and its fractions on anti-gastritic actions using the HCl/ethanol and indomethacin induced gastric lesion model and Helicobacter pylori (H. pylori). Based on the results, butanol fraction was most effective among fractions obtained from CAL. This study aims to elucidate the mechanisms of butanol fraction, and betaine as a constituent of the butanol fraction, on gastritis and anti-gastric cancer cell growth. First, we examined antioxidant properties using hydrogen peroxide and superoxide radical, and we found that butanol fraction and betaine may be good antioxidants. Second, cytotoxicity was assessed by measuring cell viability and 4,6-diamidino-2-phenylinodole dihydrochloride (DAPI) staining of human gastric cancer cells (AGS cells). We also examined the relationship between the cytotoxicity and intracellular $Ca^{2+}$ signaling mechanism. The butanol fraction demonstrated cell viability 71.49% at the concentration of 100 ${\mu}g/ml$ and increased intracellular $Ca^{2+}$ concentration in a dose dependent manner. Finally, we observed the mucus content as a defensive factor and gastric secretion as an aggressive factor, and found that the mucus content noticeably increased when treated with butanol fraction and betaine and gastric secretion decreased when treated with betaine in vivo study. From these results, we suggest that CAL butanol fraction and betaine may have protective effects on gastritis.

• Molecular Medicine Reports
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• 제21권3호
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• pp.1374-1382
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• 2020

Arctigenin is a natural lignan that is found in burdock with anti-viral, -oxidative, -inflammatory and anti-tumor activities. In the current study, the effect of arctigenin on metastatic potential was examined in 4T-1 mouse triple-negative breast cancer cells. The results indicated that arctigenin inhibited cell motility and invasiveness, which was determined using wound healing and transwell invasion assays. Arctigenin suppressed matrix metalloprotease-9 (MMP-9) activity via gelatin zymography, and protein expression of cyclooxygenase-2 (COX-2) and MMP-3. Furthermore, arctigenin attenuated the mRNA expression of metastatic factors, including MMP-9, MMP-3 and COX-2. Based on these results, the effect of arctigenin on the mitogen-activated protein kinase (MAPK)/activating protein-1 (AP-1) signaling pathway was assessed in an attempt to identify the regulatory mechanism responsible for its anti-metastatic effects. Arctigenin was demonstrated to inhibit the phosphorylation of extracellular signal-regulated protein kinase (ERK) and c-Jun N- terminal kinase (JNK), and the nuclear translocations of the AP-1 subunits, c-Jun and c-Fos. In summary, the present study demonstrated that in 4T-1 mouse triple-negative breast cancer cells the anti-metastatic effect of arctigenin is mediated by the inhibition of MMP-9 activity and by the inhibition of the metastasis-enhancing factors MMP-9, MMP-3 and COX-2, due to the suppression of the MAPK/AP-1 signaling pathway. The results of the current study demonstrated that arctigenin exhibits a potential for preventing cell migration and invasion in triple negative breast cancer.

• Journal of Applied Biological Chemistry
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• 제63권2호
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• pp.147-152
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• 2020

Farrerol은 중국에서 거담제로 사용되어온 전통 한약제로 사용된 산진달래(만산홍, Rhododendron dauricum L.)에서 유래된 플라바논이다. Farrerol은 항산화, 항염증 및 항균 작용을 포함한 다양한 생리 활성이 보고되었다. 하지만 farrerol의 MCF-7에 대한 항암 작용은 아직 보고된 바가 없다. 본 연구에서 인간 유방암 MCF-7 세포에 대한 farrerol의 처리가 세포증식을 억제하고 apoptosis를 유도함을 입증하였다. MCF-7 세포에 ferrerol을 48시간 동안 처리했을 때, 이는 통계적으로 유의한 세포증식 효과를 나타냈으며 이의 IC₅₀ 값은 145.04±1.4 μM임을 확인하였다. 또한, farrerol이 세포사멸을 유도함을 TUNEL assay와 FACS를 이용한 Annexin V/PI 염색을 통해 검증하였다. 이러한 항암 효능의 작용기전으로써, farrerol의 처리가 BAX/Bcl-2 및 Caspase-3활성화와 PARP 분절화를 증가시켜 세포자살을 촉진한다는 것을 확인하였다. 결론적으로, 본 연구의 결과는 farrerol이 apopotosis 관련 단백질의 활성 및 발현조절을 통해 MCF-7 유방암세포에 대한 항암 효능을 갖는다는 것을 보여주고 있다.

• International Journal of Oral Biology
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• 제46권4호
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• pp.160-167
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• 2021

Nypa fruticans Wurmb (NFW) contains a large amount of phenolic acid and flavonoids, and is popular as a superfood in Myanmar. NFW has various biological activities, such as anti-inflammatory, anti-oxidant, and neuroprotective properties; however, the anti-cancer effect of NFW have not been reported. In this study, we investigated the anticancer activity of water extracts of NFW (WeNFW) and the underlying mechanism in human FaDu hypopharyngeal squamous carcinoma cells. The WeNFW inhibited FaDu cell growth in a dose-dependent manner without affecting normal cells (L929), as determined by an MTT assay and Live and Dead assay. In addition, the concentrations of WeNFW without cytotoxicity (0.025, 0.05, and 0.1 mg/mL) inhibited wound healing and colony formation. Furthermore, WeNFW significantly induced apoptosis through the proteolytic cleavage of caspase-3 and -9, poly (ADP-ribose) polymerase, and downregulation of Bcl-2 and upregulation of Bax in FaDu cells, as determined by DAPI staining, FACS analysis, and western blot analysis. Taken together, these results suggest that WeNFW exhibits potent anti-cancer effects by suppressing the growth of oral cancer cells, wound healing and colony formation activity. Via mitrochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, WeNFW can provide a natural chemotherapeutic drug for oral cancer in humans.