• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1122-1126
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• 2002

We have examined whether Soamsan 1 (SA 1) augment the inhibitory effect of oral administration of Soamsan (SA) on lung metastasis of mouse 816 melanoma cells. The inhibitory effect was slightly enhanced by increase in administration dosage of SA 1. SA 1 as well as SA inhibited effectively the lung metastasis regardless of the pretreatment with anti-mouseNK monoclonal antibody. However, in the case of 2-chloroadenosine-pretreated mice, the inhibitory effects of SA and SA 1 were decreased by 18 and 23%, respectively. In vitro stimulation of the mouse splenocytes with mitogens showed that SA or SA 1 significantly augmented the proliferation of mouse splenocytes. Especially, the activity was more prominent in the presence of a B cell mitogen. LPS than a T cell mitogen, Con A. These results suggest that oral administration of SA 1 or SA inhibited lung metastasis of B16 melanoma cells, possibly through a mechanism mediated by the activation of macrophages and B lymphocytes in the host immune system. However, SA 1 did not showed more significant augment of the activation of immune system than SA.

• Toxicological Research
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• v.23 no.3
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• pp.197-205
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• 2007

Cancer metastasis is a major determinant of cancer patient mortality. Mounting evidence favors a strong positive role for $TGF-{\beta}$ in human cancer progression. The complex pattern on cross-talk of $TGF-{\beta}$ and the related other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional role of $TGF-{\beta}$ in cancer progression. This review summarizes some of the current understanding of $TGF-{\beta}$ signaling with a major focus in its contribution to the tumor cell invasion and metastasis. Five issues are addressed in this review: (1) $TGF-{\beta}$ signaling, (2) $TGF-{\beta}$ and EMT, (3) $TGF-{\beta}$ and MMP, (4) $TGF-{\beta}$ and Ras, and (5) Role of $TGF-{\beta}$ in invasion and metastasis. Due to the bifunctional cellular effects of $TGF-{\beta}$, as a tumor promoter and a tumor suppressor, more precisely defined $TGF-{\beta}$ signaling pathways need to be elucidated. According to the current literature, $TGF-{\beta}$ is clearly a major factor stimulating tumor progression through a complex spectrum of the interplay and cross-talk between various signaling molecules. Understanding the role of $TGF-{\beta}$ in invasion and metastasis will provide valuable information on establishing strategies to manipulate $TGF-{\beta}$ signaling which should be a high priority for the development of anti-metastatic therapeutics.

• Fisheries and Aquatic Sciences
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• v.15 no.1
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• pp.29-36
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• 2012

Osteosarcoma is the most common primary malignancy of bone, and patients often develop pulmonary metastasis. The mechanisms underlying osteosarcoma metastasis remain to be elucidated. Recently, anti-inflammatory agents were shown to be useful in the treatment of tumor progression. We previously isolated a natural anti-inflammatory peptide from the seahorse Hippocampus kuda bleeler. Here, we examined the antitumor metastatic activity of this peptide and investigated its mechanism. The peptide significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasive migration of human osteosarcoma MG-63 cells. Its inhibitory effect on invasive migration was associated with reduced expression of matrix metalloproteinases (MMP1 and MMP2). In addition, TPA stimulation increased intracellular reactive oxygen species (ROS) generation and small GTPase Rac1 expression, whereas the peptide decreased ROS generation and Rac1 activation. Taken together, these results suggest that the peptide inhibits invasive migration of MG-63 osteosarcoma cells by inhibiting MMP1 and MMP2 expression through downregulation of Rac1-ROS signaling.

• BMB Reports
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• v.42 no.10
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• pp.655-660
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• 2009

The potential anti-metastasis and anti-invasion activities of early growth response gene-1 (Egr-1) and claudin-3, a tight junction (TJ)-related protein, were evaluated using histone deacetylase (HDAC) inhibitors in human hepatocarcinoma cells. The results of wound healing and Transwell assays showed that HDAC inhibitors such as trichostatin A and sodium butyrate inhibited cell migration and invasion. HDAC inhibitors markedly induced Egr-1 expression during the early period, after which expression levels decreased. In addition, the down-regulation of snail and type 1 insulin-like growth factor receptor (IGF-1R) in HDAC inhibitor- treated cells induced the upregulation of thrombospondin-1 (TSP-1), E-cadherin and claudin-3. Cells transfected with Egr-1 and claudin-3 siRNA displayed significant blockage of HDAC inhibitor-induced anti-invasive activity. Collectively, these findings indicate that the up-regulation of Egr-1 and claudin-3 are crucial steps in HDAC inhibitor-induced anti-metastasis and anti-invasion.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.522-527
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• 2002

The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis shwed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the anti metastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.422-429
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• 2009

Invasion and metastasis is the main cause of cancer mortality. Angiogenesis is a prerequisite for the tumor growth and metastasis. Matrix metalloproteinases (MMPs) are the key enzymes playing in the invasive growth and metastasis of cancer as well as angiogenesis. Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L), has been reported to suppress cancer invasion and angiogenesis. In the present study, we investigated the antiinvasive effects of xanthohumol (1) and its synthetic derivatives, 4'-O-methylxanthohumol SEM ether (2), xanthohumol C (3), and xanthohumol C MOM ether (4) in relation to MMP expression in HT-1080 human fibrosarcoma cells. The compound 1 and its derivative, 3 and 4, significantly inhibited serum-induced HT-1080 cell invasion, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced activity and expression level of MMP-2 and MMP-9 in a concentration-dependant manner. In addition, they inhibited TPA-enhanced expression of MT1-MMP with relatively weak inhibition in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 level. The compound 1 significantly decreased the cell viability, whereas the derivatives, 2 and 3 showed no cytotoxicity, and compound 4 showed slight cytotoxicity in the cells. Furthermore, in a chick chorioallantoic membrane (CAM) assay, the derivatives 3 and 4 dose-dependently suppressed vascular endothelial growth factor (VEGF)-induced angiogenesis, which is similar to that of compound 1. Taken together, the results indicate that compounds 3 and 4 may be valuable anti-angiogenic agents in the treatment of chronic diseases such as cancer and inflammation working through suppression of MMP-2 and MMP-9.

• Journal of Microbiology and Biotechnology
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• v.30 no.3
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• pp.325-332
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• 2020

Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.

• The Korean Journal of Food And Nutrition
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• v.26 no.3
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• pp.375-382
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• 2013

The present study is designed to explore an anti-tumor activity on crude extracts of Oplopanax elatus. Water extractions of Oplopanax elatus were performed at $100^{\circ}C$(OeE-100). OeE-100 doses up to $62.5{\mu}g/m{\ell}$ had no cytotoxicity on the tumor cell lines in vitro. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma, the prophylactic intravenous ($4{\sim}100{\mu}g/mouse$) or oral (2 mg/mouse) administration of OeE-100 significantly inhibited tumor metastasis as compared with tumor controls. Peritoneal macrophages stimulated with OeE-100 produced various cytokines such as TNF-${\alpha}$, IL-6 and IL-12. In an analysis of NK-cell activities, i.v. administration of OeE-100 ($10{\sim}100{\mu}g/mouse$) significantly augmented the cytotoxicity to YAC-1 tumor cells. Vaccination of mice with boiling-treated tumor cells (BT-vaccine) in combination with OeE-100 ($100{\mu}g/mouse$) showed higher inhibitions in tumor metastasis when compared with the mice of BT-vaccine treatment. In addition, the splenocytes from OeE-100 admixed BT-vaccine immunized mice secreted a higher concentration of Th1 type cytokine such as IFN-${\gamma}$. These results suggested that the OeE-100 stimulated immune system and was a good candidate adjuvant of anti-tumor immune responses.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.282-289
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• 2008

We evaluated the effect of SHBCS on adhesion and invasion of colon L5-26 adenocarcinoma cell line in vitro in vitro and experimental liver metastasis in vivo. SHBCS showed little inhibitory effect on colon 26-L5 cell proliferation. At the concentration of up to 500 mg/ml of SHBCS 80% of cells were viable. SHBCS showed no inhibitory effect on adhesion and invasion of colon 26-L5 cells, which were placed on matrigel. In a dose dependent manner, oral administration of SHBCS showed a significantly inhibitory effect on liver metastasis from colon 26-L5 injected mice. When mice were depleted of NK cells or macrophages before tumor inoculation, SHBCS significantly decreased liver metastasis fromf the tumor injected mice. Compared with the control mice, SHBCS increased the populations of macrophages and NK cells by 30%, 18%(10 mg/mouse, 50 mg/mouse) and 5%, 1% (10 mg/mouse, 50 mg/mouse) respectively. Compared with the control mice, SHBCS increased the populations of CD4 cells by 5%, 18% (10 mg/mouse, 50 mg/mouse) respectively. Spelenocytes from mice administerd with SHBCS were stimulated with LPS plus ConA, proliferation of splenocytes from mice administerd with SHBCS was 140%, 146%(10 mg/mouse, 50 mg/mouse) compared with th control mice. In conclusion, the present study suggests that SHBCS may have an inhibitory effect on liver metastasis through immunopotentiating activity which is associated with macrophages and NK cells.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.363-374
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• 2010

Growing evidence suggests a prominent role for leptin in human cancer progression. The intricate pattern of leptin cross-talk with other associated signaling pathways is a critical area of research that will ultimately contribute to comprehending the role of leptin in cancer progression. This review summarizes a portion of the current understanding of leptin signaling, with a critical focus on its contribution to tumor cell invasion and metastasis. Five topics are addressed in this review: (1) Leptin receptor, (2) Leptin signaling, (3) Leptin and cancer, and (4) Leptin and tumor invasion. Due to the complex cellular effects of leptin, a more precise understanding of leptin signaling pathways must still be elucidated. Leptin is clearly a major factor for stimulating tumor progression through a complex spectrum of interplay and cross-talk among various signaling molecules. An understanding of the role of leptin in invasion and metastasis will provide valuable information for establishing strategies to modulate leptin signaling, which should be a high priority for the development of anti-cancer therapeutics.