• BMB Reports
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• v.57 no.6
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• pp.273-280
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• 2024

Cancer cells metastasize to distant organs by altering their characteristics within the tumor microenvironment (TME) to effectively overcome challenges during the multistep tumorigenesis. Plasticity endows cancer cell with the capacity to shift between different morphological states to invade, disseminate, and seed metastasis. The epithelial-to-mesenchymal transition (EMT) is a theory derived from tissue biopsy, which explains the acquisition of EMT transcription factors (TFs) that convey mesenchymal features during cancer migration and invasion. On the other hand, adherent-to-suspension transition (AST) is an emerging theory derived from liquid biopsy, which describes the acquisition of hematopoietic features by AST-TFs that reprograms anchorage dependency during the dissemination of circulating tumor cells (CTCs). The induction and plasticity of EMT and AST dynamically reprogram cell-cell interaction and cell-matrix interaction during cancer dissemination and colonization. Here, we review the mechanisms governing cellular plasticity of AST and EMT during the metastatic cascade and discuss therapeutic challenges posed by these two morphological adaptations to provide insights for establishing new therapeutic interventions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5747-5751
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• 2014

Background: Coptisine, an isoquinoline alkaloid extracted from Coptidis rhizoma, has many biological activities such as antidiabetic, antimicrobial and antiviral actions. However, whether coptisine exerts anti-cancer metastasis effects remains unknown. Materials and Methods: Effects of coptisine on highly metastatic human breast cancer cell MDA-MB-231 proliferation were evaluated by trypan blue assay and on cell adhesion, migration and invasion by gelatin adhesion, wound-healing and matrigel invasion chamber assays, respectively. Expression of two matrix metalloproteinases (MMPs), MMP-9, MMP-2 and their specific inhibitors tissue inhibitor of metalloproteinase 1 (TIMP-1) and tissue inhibitor of metalloproteinase 2 (TIMP-2) were analyzed by RT-PCR. Results: Coptisine obviously inhibited adhesion to an ECM-coated substrate, wound healing migration, and invasion through the matrigel in MDA-MB-231 breast cancer cells. RT-PCR revealed that coptisine reduced the expression of the ECM degradation-associated gene MMP-9 at the mRNA level, and the expression of TIMP-1 was upregulated in MDA-MB-231 cells, while the expression of MMP-2 and its specific inhibitor TIMP-2 was not affected. Conclusions: Taken together, our data showed that coptisine suppressed adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function. Coptisine might be a potential drug candidate for breast cancer therapy.

• Korean Journal of Head & Neck Oncology
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• v.25 no.1
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• pp.3-7
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• 2009

Background and Objectives : Panax ginseng C.A. Meyer is a medical plant that has been widely utilized as a tonic and nutritional agent since ancient times in Korea. Ginseng has anti-metastatic property of cancer and immunomodulating activity. The novel acidic polysaccharide compound(MB40) was isolated from the leaves of Panax ginseng C.A. Meyer. To determine immunomodulating activities of MB40, we evaluate anti-cancer and anti-metastatic effects of MB40 in tumor bearing immune competent mice. Material and Methods : C3H mice were divided into three equal groups(Cisplatin treatment group, MB40 treat-ment group, Cisplatin and MB40 treatment group) and were transplanted SCC(Squamous Cell Carcinoma) cells(2${\times}$106) to the lateral side of abdomen. From day 4 after transplantation, MB40 was administrated at dose of 10mg/kg, respectively, every other day by intratumoral injection. Cisplatin was systemically administrated at doses of 1mg/kg, respectively, every week by intraperitoneal injection. Results : 5 days after administration, tumors can be palpated in every mice group. After 13 days of administration, the mice group to which MB40 were administrated exhibited reduction in tumor size respectively, compared to cisplatin group. Overall status of mice such as body weight and activity were superior in MB40 group than cisplatin group. Conclusion : The result of this study indicates MB40 may have significant therapeutic effect and decreases complications induced by systemic chemotheraphy. MB40 may be developed as a novel and potent immunotropics to improve the cell immune system and anti-cancer drug for the treatment of cancer patients in head and neck squamous cell carcinoma.

• Journal of Gastric Cancer
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• v.23 no.1
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• pp.224-249
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• 2023

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1608-1612
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• 2004

This study was conducted to investigate angiogenic inhibitory effect of Zingiberis Rhizoma methanol extract using ECV-304 cells and HT1080 fibrosarcoma cells. The viability of ECV-304 was 30% at 50㎍/㎖ of Zingiberis extract and that of HT1080 was 30% at 100㎍/㎖. Using the BrdU incorporation assay, Zingiberis inhibited the DNA synthesis of ECV-304 and HT1080 by 70% and 50% at 200㎍/㎖. In tube formation assay, at 10㎍/㎖ of Zingiberis, tube network began to degrade and at higher doses, it was completely destroyed. Zymography demonstrated that Zingiberis extract decreased MMP-9 at 10㎍/㎖ and higher doses remarkably inhibited the expression of MMP-9. These data indicate that Zingiberis Rhizoma has angiogenic inhibitory effects and shows the possibility of future anti-metastatic drug.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10351-10354
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• 2015

Background: Rosa Roxburghii Tratt is a promising wild fruit crop in Southwest China. Its extracts have been used as traditional Chinese medicine, which benefit immune responses and cure various health disorders. However, whether Rosa Roxburghii Tratt polysaccharides could inhibit metastasis and invasion of ovarian cancer cells remains unknown. Materials and Methods: Effects of crude polysaccharides from Rosa Roxburghii Tratt on the viability of ovarian cancer A2780 cells were detected by MTT assay. Ovarian carcinoma cell migration and invasion after exposure to Rosa Roxburghii Tratt polysaccharides were quantified by wound healing and Transwell assays, respectively. Western blotting was applied to assess protein levels of MMP-9. Results: The results indicated that Rosa Roxburghii Tratt polysaccharides significantly reduced wound closure rate of A2780 cells, inhibited their migration and invasion, and suppressed the expression of MMP-9. Conclusions: Our findings indicated that Rosa Roxburghii Tratt polysaccharides have potential for develop as anti-metastatic cancer drug preparations for ovarian cancer patients.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.29-35
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• 2019

Decursin is a major biological active component of Angelica gigas Nakai and is known to induce apoptosis of metastatic prostatic cancer cells. Recently, other reports have been commissioned to examine the anticancer activities of this plant. In this study, we evaluated the inhibitory activity and related mechanism of action of decursin against glioblastoma cell line. Decursin demonstrated cytotoxic effects on U87 and C6 glioma cells in a dose-dependent manner but not in primary glial cells. Additionally, decursin increased apoptotic bodies and phosphorylated JNK and p38 in U87 cells. Decursin also down-regulated Bcl-2 as well as cell cycle dependent proteins, CDK-4 and cyclin D1. Furthermore, decursin-induced apoptosis was dependent on the caspase activation in U87 cells. Taken together, our data provide the evidence that decursin induces apoptosis in glioblastoma cells, making it a potential candidate as a chemotherapeutic drug against brain tumor.

• Journal of Medicine and Life Science
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• v.15 no.2
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• pp.46-50
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• 2018

Cancer, a leading mortality disease following cardiovascular disease worldwide, has high incidence as one out of every four adults in Korea. It was known to be caused by several reasons including somatic mutation, activation of oncogene and chromosome aneuploidy. Cancer cells show a faster growth rate and have metastatic and heterogeneous cell populations compared to normal cells. Cancer stem cells, the most invested field in cancer biology, is a theory to explain heterogeneous cell populations of cancer cells among several characteristics of cancer cells, which is providing the theoretical background for incidence of cancer and treatment failure by drug resistance. Cancer stem cells initially explain heterogeneous cell populations of cancer cells based on the same markers of normal stem cells in cancer, in which only cancer stem cells showed heterogeneity of cancer cells and tumor initiating ability of leukemia. Based on these results, cancer stem cells were reported in various solid cancers such as breast cancer, liver cancer, and lung cancer. Breast cancer stem cells were first reported in solid cancer which had tumor initiating ability and further identified as anti-cancer drug resistance. There were several identification methods in breast cancer stem cells such as specific surface markers and culture methods. The discovery of cancer stem cells not only explains heterogeneity of cancer cells, but it also provides theoretical background for targeting cancer stem cells to complete elimination of cancer cells. Many institutes have been developing new anticancer drugs targeting cancer stem cells, but there have not been noticeable results yet. Many researchers also reported a necessity for improvement of current concepts and methods of research on cancer stem cells. Herein, we discuss the limitations and the perspectives of breast cancer stem cells based on the current concept and history.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7045-7056
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• 2013

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.856-859
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• 2007

We have investigated the antimetastatic and antitumor effects of Ginsenoside Rh2 and ${\beta}-glucan$ unsing an experimental metastatic mouse model intravenously injected with B 16 melanoma F 10 cells. Animal groups are divided into six groups according to the dosage of drug administration and the kind of drugs. The groups are control, ${\beta}-glucan$ with 50, 100 and 200 mg/kg, Geinsenoside Rh2 50 mg/kg, and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg. Oral administration of various concentration of ${\beta}-glucan$( 50, 100, and 200 mg/kg) were reduced the lung- metastatics induced by metastatic B16 melanoma F 10 cells injection with a dose dependent manner in the syngenic mice. At same dosage group, Ginsenoside Rh2 (50 mg/kg) has more antimetastatic effect than the ${\beta}-glucan$(50 mg/kg). The highest antimetastatic effects was observed in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group and has a similar tendency in the anti-tumor effects, including decrease of the average tumor weight and increase of the average survival rate. There are no differences of the average tumor weights were apparent in the ${\beta}-glucan$ groups, however there were little decrease of the average tumor weight in Ginsenoside 50 mg/kg group and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group than that of the control group. The rate of average survival rate in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group, ${\beta}-glucan$ 200 mg/kg, ${\beta}-glucan$ 100 mg/kg and ${\beta}-glucan$ 50 mg/kg, and Ginsenoside 50 mg/kg groups were highly in order. These data suggest that antimetastatic and antitumor effect of combination of Ginsenodide Rh2 and ${\beta}-glucan$ be the highest in this study.