• The Journal of the Korean bone and joint tumor society
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• v.13 no.2
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• pp.88-95
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• 2007

Purpose: The purpose of this study was to compare the proapoptotic effects of matrix metal-loproteinase inhibitor (MMPI) and doxorubicin on wild-type p53 osteosarcoma cell line, socalled U2OS cell line. Materials and Methods: U2OS cells were treated with MMP inhibitor III (MMPI III) and doxorubicin, either respectively or simultaneously. In cells treated with doxorubicin, Fas-neutralizing antibody so called ZB4 was additionally treated to examine whether the doxorubicin played a role through the Fas/FasL pathway. Cells were analysed regarding to apoptosis and cell death by flow cytometry. Results: U2OS cells incubated with doxorubicin showed significant amount of cell death in dose-dependent manner. However, those incubated with MMPI III mostly remained viable state. In addition, there is no relationship between two drugs. Cells treated with doxorubicin and ZB4 at the same time did not show down regulation of apoptosis through inhibition of Fas/FasL pathway. Conclusion: It is important to re-examine MMP inhibitor's effect on other osteosarcoma cell line with wild-type p14 as well as wild-type p53 to evaluate its proapoptotic effect.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.965-970
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• 2015

Colorectal cancer is one of the most severe subtypes of cancer, and has the highest propensity to manifest as metastatic disease. Because of the lack of knowledge of events that correlate with tumor cell migration and invasion, few therapeutic options are available. The current study aimed to explore the mechanism of colorectal cancer in hope of identifying the ideal target for future treatment. We first discovered the pro-tumor effect of a controversial cell cycle regulator, cylin-dependent kinase inhibitor 3 (CDKN3), which is highly expressed in colorectal cancer, and the possible related signaling pathways, by bioinformatics tools. We found that CDKN3 had remarkable effects in suppressing colorectal cancer cell proliferation and migration, inducing cell cycle arrest and apoptosis in a colorectal cancer cell line, SW480 cells. Our study, for the first time, provided consistent evidence showing overexpression of cell cycle regulator CDKN3, in colorectal cancer. The in vitro studies in SW480 cells revealed a unique role of CDKN3 in regulating cellular behavior of colorectal cancer cells, and implied the possibility of targeting CDKN3 as a novel treatment for colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4571-4576
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• 2015

Background: To investigate the inhibitory effect and the underlying mechanism of triptolide on cultured human endometrial carcinoma HEC-1B cells and corresponding xenograft. Materials and Methods: For in vitro studies, the inhibition effect of proliferation on HEC-1B cell by triptolide was determined by MTT assay; cell cycle and apoptosis of the triptolide-treated and untreated cells were detected by flow cytometry. For in vivo studies, a xenograft tumor model of human endometrial carcinoma was established using HEC-1B cells, then the tumor-bearing mice were treated with high, medium, and low-dose ($8{\mu}g$, $4{\mu}g$ and $2{\mu}g/day$) triptolide or cisplatin at $40{\mu}g/day$ or normal saline as control. The mice were treated for 10-15 days, during which body weight of the mice and volume of the xenograft were weighted. Then expression of Bcl-2 and vascular endothelial growth factor (VEGF) was analyzed by SABC immunohistochemistry. Results: Cell growth was significantly inhibited by triptolide as observed by an inverted phase contrast microscope; the results of MTT assay indicated that triptolide inhibits HEC-1B cell proliferation in a dose and time-dependent manner; flow cytometry showed that low concentration (5 ng/ml) of triptolide induces cell cycle arrest of HEC-1B cells mainly at S phase, while higher concentration (40 or 80 ng/ml) induced cell cycle arrest of HEC-1B cells mainly at G2/M phase, and apoptosis of the cells was also induced. High-dose triptolide showed a similar tumor-inhibitory effect as cisplatin (-50%); high-dose triptolide significantly inhibited Bcl-2 and VEGF expression in the xenograft model compared to normal saline control (P<0.05). Conclusions: triptolide inhibits HEC-1B cell growth both in vitro and in mouse xenograft model. Cell cycle of the tumor cells was arrested at S and G2/M phase, and the mechanism may involve induction of tumor cell apoptosis and inhibition of tumor angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3773-3778
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• 2013

Increased oxidative stress and changes in DNA methylation are frequently detected in bladder cancer patients. We previously demonstrated a relationship between increased oxidative stress and hypomethylation of the transposable long-interspersed nuclear element-1 (LINE-1). Promoter hypermethylation of a tumor suppressor gene, runt-related transcription factor 3 (RUNX3), may also be associated with bladder cancer genesis. In this study, we investigated changes of DNA methylation in LINE-1 and RUNX3 promoter in a bladder cancer cell (UM-UC-3) under oxidative stress conditions, stimulated by challenge with $H_2O_2$ for 72 h. Cells were pretreated with an antioxidant, tocopheryl acetate for 1 h to attenuate oxidative stress. Methylation levels of LINE-1 and RUNX3 promoter were measured by combined bisulfite restriction analysis PCR and methylation-specific PCR, respectively. Levels of LINE-1 methylation were significantly decreased in $H_2O_2$-treated cells, and reestablished after pretreated with tocopheryl acetate. Methylation of RUNX3 promoter was significantly increased in cells exposed to $H_2O_2$. In tocopheryl acetate pretreated cells, it was markedly decreased. In conclusion, hypomethylation of LINE-1 and hypermethylation of RUNX3 promoter in bladder cancer cell line was experimentally induced by reactive oxygen species (ROS). The present findings support the hypothesis that oxidative stress promotes urothelial cell carcinogenesis through modulation of DNA methylation. Our data also imply that mechanistic pathways of ROS-induced alteration of DNA methylation in a repetitive DNA element and a gene promoter might differ.

• Journal of Pharmacopuncture
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• v.9 no.3 s.21
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• pp.79-88
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• 2006

Objectives : This systematic review summarizes the existing evidence on anti-tumor herbal acupuncture in South Korea. Methods : Literature searches were conducted in four databases. All studies of anti-tumor herbal acupuncture which has been published in South Korea until May, 2006 were included. Data were extracted according to pre-defined criteria by two independent reviewers. Results : We found 73 papers related to anti-tumor herbal acupuncture in South Korea. Seventy of seventy-three papers are trial research and only three papers are clinical research. Herb materials which were used in those papers are Bee-venom, Wild-ginseng, Ginseng, Houttuynia cordata Thunb, Lonicerae Flos, Carthami Tinctorii Juglans sinensis, Euphorbiae Radix, Ecliptae Herba, Crotonis Semen, Juglans sinensis, Armeniaceae Amarum, so on. From those papers, Anti-tumor herbal acupunctures are effective to tumor cell line and tumor in vivo. Clinical research papers reported that Anti-tumor herbal acupunctures are useful to improve cancer related symptoms and quality of life(QOL) of cancer patients. Conclusions : From the above results, we make sure of that anti-tumor herbal acupuncture is useful therapeutics for cancer patients. If we conceive complex-herb materials and carry out more advanced research, Anti-tumor Herbal Acupuncture is one of those major therapeutics to improve clinical symptoms and quality of life(QOL) of cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.785-791
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• 2014

Crude extracts or phytochemicals obtained from some plants have potential anti-cancer properties. Teucrium persicum is an Iranian endemic plant belonging to the Lamiaceae family which has traditionally been used to relieve abdominal pains. However, the anti-cancer properties of this species of the Teucrium genus have not been investigated previously. In this study, we have used a highly invasive prostate cancer cell line, PC-3, which is an appropriate cell system to study anti-tumor properties of plants. A methanolic extract obtained from T persicum potently inhibited viability of PC-3 cells. The viability of SW480 colon and T47D breast cancer cells was also significantly decreased in the presence of the T persicum extract. Flow cytometry suggested that the reduction of cell viability was due to induction of apoptosis. In addition, the results of wound healing and gelatin zymography experiments supported anti-cell invasion activity of T persicum. Interestingly, sublethal concentrations of T persicum extract induced an epithelial-like morphology in a subpopulation of cells with an increase in E-Cadherin and ${\beta}$-Catenin protein levels at the cell membrane. These results strongly suggest that T persicum is a plant with very potent anti-tumor activity.

• BMB Reports
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• v.47 no.2
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• pp.104-109
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• 2014

FAM176A (family with sequence similarity 176 member A) is a novel molecule related to programmed cell death. A decreased expression of FAM176A has been found in several types of human tumors in including lung cancers. In the present study, we investigated the biological activities of FAM176A on the human non-small cell lung cancer cell line H1299 cells. We constructed a recombinant adenovirus 5-FAM176A vector (Ad5-FAM176A) and evaluated the expression and anti-tumor activities in vitro. Cell viability analysis revealed that the adenovirus-mediated increase of FAM176A inhibited the growth of the tumor cells in a dose- and time-dependent manner. This inhibitory effect was mediated by both autophagy and apoptosis that involved caspase activation. In addition, cell cycle analysis suggested that Ad5-FAM176A could induce cell cycle arrest at the G2/M phase, all of which suggested that adenovirus-mediated FAM176A gene transfer might present a new therapeutic approach for lung cancer treatment.

• Journal of Microbiology and Biotechnology
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• v.16 no.12
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• pp.1919-1927
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• 2006

Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but various unexpected side effects are observed, which may result from the bulk activation of various bystander cells. In this study, we tested tumor vaccines expressing various membrane-bound forms of IL-2 (mbIL-2) on MethA fibrosarcoma cells to focus antitumor immune responses to CTL. Chimeric forms of IL-2 with whole CD4, deletion forms of CD4, and TNF were expressed on the tumor cell surface, respectively. Tumor clones expressing mbIL-2 or secretory form of IL-2 were able to support the cell growth of CTLL-2, an IL-2-dependent T cell line, and the proliferation of spleen cells from 2C TCR transgenic mice that are responsive to the $p2Ca/L^d$ MHC class I complex. Expression of mbIL-2 on tumor cells reduced the tumorigenicity of tumor cells, and the mice that once rejected the live IL-2/TNF tumor clone acquired systemic immunity against wild-type MethA cells. The IL-2/TNF clone was inferior to other clones in tumor formation, and superior in the stimulation of the CD8+ T cell population in vitro. These results suggest that the IL-2/TNF clone is the best tumor vaccine, and may stimulate CD8+ T cells by direct priming. Expression of IL-2/TNF on tumor cells may serve as an effective gene therapy method to ameliorate the side effects encountered in the recombinant cytokine therapy and the conventional cytokine gene therapy using the secretory form of IL-2.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.234-250
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• 1998

Bujeonghangamtang(扶正抗癌湯) has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carroed out to evaluate the possible therapeutic or antitumoral effects of Bujeonghangamtang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by .the typical application of 3-methylcholanthrene (MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(Sl80 cells). Treatment of the Bujeonghangamtang water-extract (dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Bujeonghangamtang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice (TBM). Bujeongmngamtang also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurence-frequency and their size, and some developed tumors were regressed by the continuous treatment of Bujeonghangamtang extract into TBM. In vitro, treatment of Bujeonghangamtang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Bujeonghangamtang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Bujeonghangamtang-administration to mice enhanced NK cells attivities. These results demonstrated that Bujeonghangamtang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Bujeonghangamtang might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.99-99
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• 2003

We studied the effect of Rubus croceacanthus Leveille (RCL) on mast cell-mediated anaphylactic reactions. RCL inhibited compound 48/80-induced systemic anaphylactic shock. When RCL was given at concentrations ranging from 0.01 to 1 mg/$m\ell$, the histamine release from rat peritoneal mast cells induced by compound 48/80 was reduced in a dose-dependent manner. RCL also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. In addition, RCL inhibited phorbol 12-myristate 13-acetate and A23187-induced tumor necrosis factor-${\alpha}$ secretion from human mast cell line HMC-1 cells. These results indicate that RCL may possess a strong anti-anaphylactic activity.