• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3071-3075
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• 2016

Morin, a flavonoid found in figs and other Moraceae species, displays a variety of biological actions, exerting anti-oxidant, anti-inflammatory and anti-carcinogenic effects. Here, we investigated the anti-cancer activity of morin focusing on anti-adhesive influence. We performed experiments with MDA-MB-231 human breast cancer cells. Morin inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. It further inhibited the expression of VCAM-1 on MDA-MB-231 cells as well as HUVECs. Morin also decreased the expression of N-cadherin on MDA-MB-231 cells. In addition, there was apparent anti-metastatic activity in vivo. In conclusion, this study suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM-1, and EMT by targeting N-cadherin, and that it features anti-metastatic activity in vivo. Further investigation of possible anti-metastatic activity of morin against human breast cancer cells is warranted.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.581-590
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• 2016

Resistance to anoikis, a cell-detachment induced apoptosis, is one of the malignant phenotypes which support tumor metastasis. Molecular mechanisms underlying the establishment of this phenotype require further investigation. This study aimed at exploring protein expression profiles associated with anoikis resistance of a metastatic breast cancer cell. Cell survival of suspension cultures of non-metastatic MCF-7 and metastatic MDA-MB-231 cells were compared with their adherent cultures. Trypan blue exclusion assays demonstrated a significantly higher percentage of viable cells in MDA-MB-231 than MCF-7 cell cultures, consistent with analysis of annexin V-7-AAD stained cells indicating that MDA-MB-231 possess anti-apoptotic ability 1.7 fold higher than MCF-7 cells. GeLC-MS/MS analysis of protein lysates of MDA-MB-231 and MCF-7 cells grown under both culture conditions identified 925 proteins which are differentially expressed, 54 of which were expressed only in suspended and adherent MDA-MB-231 but not in MCF-7 cells. These proteins have been implicated in various cellular processes, including DNA replication and repair, transcription, translation, protein modification, cytoskeleton, transport and cell signaling. Analysis based on the STITCH database predicted the interaction of phospholipases, PLC and PLD, and 14-3-3 beta/alpha, YWHAB, with the intrinsic and extrinsic apoptotic signaling network, suggesting putative roles in controlling anti-anoikis ability. MDA-MB-231 cells grown in the presence of inhibitors of phospholipase C, U73122, and phospholipase D, FIPI, demonstrated reduced ability to survive in suspension culture, indicating functional roles of PLC and PLD in the process of anti-anoikis. Our study identified intracellular mediators potentially associated with establishment of anoikis resistance of metastatic cells. These proteins require further clarification as prognostic and therapeutic targets for advanced breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4555-4559
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• 2012

Breast cancer causes death due to distant metastases in which tumor cells produce matrix metalloproteinase (MMP) enzymes which facilitate invasion. Oleuropein, the main olive oil polyphenol, has anti-proliferative effects. This study aimed to investigate the effect of oleuropein on the metastatic and anti-metastatic gene expression in the MDA human breast cancer cell line. We evaluated the MMPs and TIMPs gene expression by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in treated and untreated cells. This study demonstrated that OL may induce anti-metastatic effects on human breast cancer cells. We found that TIMP1,-3, and -4 were over-expressed after all periods of incubation in treated cancer cells compared to untreated cells, while MMP2 and MMP9 genes were down-regulated, at least initially. Treatment of breast cancer cells with oleuropein could help in prevention of cancer metastasis by increasing the TIMPs and suppressing the MMPs gene expressions.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.92-98
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• 2010

Breast cancer has been estimated as one of the most common causes of cancer death among women. The major cause of death from breast cancer is the metastatic spread of the disease from the primary tumor to distant sites in the body. Lycopene is one of the major carotenoids in fruits and vegetables including tomatoes. Epidemiological studies have shown that the dietary intake of lycopene is associated with decreased risk of cancer. Although mounting evidence shows the chemopreventive effect of lycopene, the role of lycopene in the prevention of metastatic potential of breast cancer has not been determined yet. In the present study, we investigated the inhibitory effect of lycopene on invasive and migratory phenotypes of two highly aggressive breast cancer cell lines, H-Ras-transformed MCF10A human breast epithelial cells (H-Ras MCF10A) and MDA-MB-231 human breast cancer cells. Here, we report that lycopene significantly inhibits invasion and migration as well as proliferation of H-Ras MCF10A and MDA-MB-231 cells. This study suggested an in vitro anti-cancer and anti-metastatic potential of lycopene. We also showed that activations of ERKs and Akt were inhibited by lycopene in H-Ras MCF10A cells, suggesting that the ERKs and Akt signaling pathways may be involved in lycopene-induced anti-proliferative and/or anti-invasive/migratory effects in these cells. Taken in conjunction with the fact that breast cancer metastasis is one of the most lethal malignancies in women, our findings may provide useful information for the application of lycopene in establishing strategy to prevent the metastatic breast cancer.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.3
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• pp.59-67
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• 2023

Purpose : Epithelial-to-mesenchymal transition (EMT) is recognized as an important cellular response in metastatic proceduresand characterized by loss of cellular polarity as well as gain of mesenchymal features, which enables migration and invasion. Hepatocellular carcinoma (HCC) is one of the most common primary carcinomas in the liver and exhibits a poor prognosis due to frequent extrahepatic metastasis. Taraxacum officinale has been used for a long time in oriental medicine because of its various pharmacological activitiessuch as anti-rheumatic, anti-inflammatory, antioxidative, and anticarcinogenic activities. In this study, the anti-metastatic activity of T. officinale water extract (TOWE) and ethanol extract (TOEE) was investigated through the regulation of EMT in the Huh7 cells. Methods : The effects of TOWE and TOEE on migratory and invasive activities were investigated by wound healing and in vitro invasion assays. Western blot analysis was also applied to analyze protein expression levels associated with EMT and their upstream transcription factors in Huh7 cells. Results : TOWE and TOEE treatment potently inhibited migration and invasion of Huh7 cells compared to the untreated group. Both extracts treatment inhibited protein expression levels of N-cadherin, matrix metalloproteinase (MMP)-9, and vimentin while E-cadherin was significantly accelerated. In addition, the activated status of transcription factors, Snail, nuclear factor (NF)-κ B, and zinc finger E-box binding homeobox (ZEB)1 was also inhibited with statistical significance. In comparison to both extracts, TOEE more potently attenuated migration, invasion, and EMT markers as well as their transcription factors in Huh7 cells than TOWE, which means that TOEE might possess more functional phytochemicals than TOWE. Conclusion : Consequently, TOWE and TOEEattenuated metastatic activity of hepatocellular carcinoma through the regulation of EMT markers and their transcription factors in Huh7 cells, which means that T. officinale might be a promising strategy for a chemopreventive agent against HCC metastasis.

• Korean Journal of Pharmacognosy
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• v.31 no.4
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• pp.394-400
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• 2000

Tumor cell interaction with the extracellular matrix (ECM) is defined as the critical event of tumor invasion that signals the initiation of a metastatic cascade. To search for anti-metastatic agent from plants, several plant extracts were screened by cell- ECM anti-adhesion test. As result, Boehmeria pannosa, Dryopteris crassirhizoma, Scilla scilloides, and Agrimonia pilosa were shown a significant anti-adhesion activity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2729-2734
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• 2012

Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects. Oroxylum indicum (L.) Vent. is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties. In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA-MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay. All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells. PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells. Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects. Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity. Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1833-1840
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• 2013

Metastasis is one of the hallmarks of malignant neoplasms and is the leading cause of death in many cancer patients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastasis. In this study, the anti-metastatic potential of the methanolic extract of Rhizophora apiculata (R.apiculata) was evaluated using the B16F-10 melanoma induced lung metastasis model in C57BL/6 mice. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with R.apiculata extract (10 mg/kg b.wt (intraperitoneal) significantly (p<0.01) inhibited pulmonary tumor nodule formation (41.1 %) and also increased the life span (survival rate) 107.3 % of metastatic tumor bearing animals. The administration of R.apiculata extract significantly (p<0.01) reduced biochemical parameters such as lung collagen hydroxyproline, hexosamine, uronic acid content, serum nitric oxide (NO), ${\gamma}$-glutamyl transpeptidase (GGT) and sialic acid levels when compared to metastasis controls. These results correlated with lung histopathology analysis of R.apiculata extract treated mice showing reduction in lung metastasis and tumor masses. Taken together, our findings support that R.apiculata extract could be used as a potential anti-metastasis agent against lung cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1686-1693
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• 2004

Ekong-san(EKS) was expected to have inhibitory effects on angiogenesis, considering the fact that its constituents such as Ginseng Radix, Glycyrrhizae Radix and Citri Pericarpium were reported to inhibit angiogenesis. Moreover, recently several metabolites transformed by the human intestinal microflora were reported to enhance effectiveness compared to their crude drugs. Based on these data, this study was designed to confirm whether the EKS metabolites (EKS-M) can significantly exert the anti-angiogenic and anti-metastatic activites. Hence, with EKS and EKS-M, viability assay, proliferation assay, in vitro tube formation assay, gelatin zymogram assay, in vitro invasion assay were carried out. EKS showed less toxicity in ECV304 and HT1080 cells than EKS-M. EKS-M inhibited the proliferation of HT1080 cells by 30% at 200㎍/㎖ and 42% at 400 ㎍/㎖ respectively. Also, EKS-M degraded the tube network at 200㎍/㎖. EKS and EKS-M inhibited the expression of MMP-9 at 200 and 400㎍/㎖ in HT1080 cells. EKS reduced the invasive activity of HT1080 cells through matrigel coated transfilter atthe concentration of 200㎍/㎖ more effectively than EKS-M. These data suggest that EKS and EKS-M has anti-angiogenic and anti-metastatic activities.

• Molecules and Cells
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• v.39 no.5
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• pp.403-409
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• 2016

NME1 is a well-known metastasis suppressor which has been reported to be downregulated in some highly aggressive cancer cells. Although most studies have focused on NME1, the NME1 gene also encodes the protein (NME1L) containing N-terminal 25 extra amino acids by alternative splicing. According to previous studies, NME1L has potent anti-metastatic activity, in comparison with NME1, by interacting with $IKK{\beta}$ and regulating its activity. In the present study, we tried to define the role of the N-terminal 25 amino acids of NME1L in $NF-{\kappa}B$ activation signaling. Unfortunately, the sequence itself did not interact with $IKK{\beta}$, suggesting that it may be not enough to constitute the functional structure. Further construction of NME1L fragments and biochemical analysis revealed that N-terminal 84 residues constitute minimal structure for homodimerization, $IKK{\beta}$ interaction and regulation of $NF-{\kappa}B$ signaling. The inhibitory effect of the fragment on cancer cell migration and $NF-{\kappa}B$-stimulated gene expression was equivalent to that of whole NME1L. The data suggest that the N-terminal 84 residues may be a core region for the anti-metastatic activity of NME1L. Based on this result, further structural analysis of the binding between NME1L and $IKK{\beta}$ may help in understanding the anti-metastatic activity of NME1L and provide direction to NME1L and $IKK{\beta}$-related anti-cancer drug design.