• Radiation Oncology Journal
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• v.14 no.4
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• pp.255-264
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• 1996

Purpose : Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cell cycle in $G_2$-M Because $G_2$-M is the most radiosensitive Phase of the cell cycle, paclitaxel has potential as a cell cycle- specific radiosensitizer. This study was designed to investigate the ability of paclitaxel to increase the radiotoxicity in normal small bowel mucosa of the rat. materials and Methods : A sigle intraperitoneal infusion of paclitaxel (10mg/kg), and a single irradiation(8 Gy, x-ray) to the whole abdomen and combination of radiation(8 Gr, x-ray) 24 hours after paclitaxel infusion in the rats were done. The changes of jejunal mucosa, and kinetics of mitotic arrest and apoptosis in the jejunal crypt were defined at 6 hours - 5 days after each treatment histologically. Results : Paclitaxel blocked jejunal crypt cell in mitosis and induced minmal apoptosis. Mitotic arrest by paclitaxel was peaked at 6 hours after infusion and returned to normal by 24 hours. Radiation induced apoptosis and peaked at 6 hours and returned to normal by 24 hours. Combination of paclitaxel and radiation blocked crypt cell in mitosis at 3 days and induced apoptosis slightly at 6 hours and 24 hours and returned to normal by 3 days. The incidence of apoptosis in combined group at 6 hours was slightly higher than normal control but significantly lower than radiation alone group. The major changes of jejunal mucosa were nuclear vesicle and atypia which were appeared at 6 hours - 3 days and returned to normal by 5 days The degree of the mucosal changes are not different in 3 groups except for absence of inflmmatory reaction in radiation group. Conclusion : Mitotic arrest by paclitaxel was peaked at 6 hours and returned to normal by 24 hours and paclitaxel induced minimal apoptosis. Radiation induced apoptosis, peaked at 6 hours and returned to normal by 24 hours. Radiation-induced apoptosis was less in combined group which suggested that paclitaxel have a radioprotective effect when radiation was given 24 hours after paclitaxel infusion.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.19-34
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• 2015

Objectives: This study was performed to investigate the anti-tumor effect of O. japonicus extracts on intrahepatic cholangiocarcinoma cell line SNU-1079. Methods: Cholangiocarcinoma SNU-1079 cells were treated with various concentrations of O. japonicus DW and EtOH extracts ($0-300{\mu}g/ml$) for 24, 48 or 72 h. Cell viability was evaluated through a PMS/MTS assay, and the apoptosis rate was examined through ELISA assay and flow cytometry analysis. The mRNA expression of apoptosis- and cell cycle progression-related genes (Bcl-2, Mcl-1, Bax, Survivin, Cyclin D1, and p21) was evaluated using real-time PCR, and the caspase activity was examined using immunoblot analysis. Results: O. japonicus extracts inhibited cell proliferation and increased apoptosis rate in both ELISA assay and flow cytometry analysis. O. japonicus extracts decreased Bcl-2, Mcl-1, Survivin, and Cyclin D1 mRNA expression and increased Bax mRNA level. O. japonicus extracts also increased Caspase-3 activation. Overall, O. japonicus DW extracts were more effective than EtOH extracts. Conclusions: O. japonicus inhibited cell proliferation and induced apoptosis in SNU-1079 cells via mitochondria -mediated intrinsic pathway, which leads to Caspase-3 activation. The results indicate that O. japonicus is a potential therapeutic herb with anti-tumor effect against intrahepatic cholangiocarcinoma.

• 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.

• Natural Product Sciences
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• v.21 no.4
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• pp.282-288
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• 2015

Viriditoxin is a fungal metabolite isolated from Paecilomyces variotii, which was derived from the giant jellyfish Nemopilema nomurai. Viriditoxin was reported to inhibit polymerization of FtsZ, which is a key protein for bacterial cell division and a structural homologue of eukaryotic tubulin. Both tubulin and FtsZ contain a GTP-binding domain, have GTPase activity, assemble into protofilaments, two-dimensional sheets, and protofilament rings, and share substantial structural identities. Accordingly, we hypothesized that viriditoxin may inhibit eukaryotic cell division by inhibiting tubulin polymerization as in the case of bacterial FtsZ inhibition. Docking simulation of viriditoxin to ${\beta}-tubulin$ indicated that it binds to the paclitaxel-binding domain and makes hydrogen bonds with Thr276 and Gly370 in the same manner as paclitaxel. Viriditoxin suppressed growth of A549 human lung cancer cells, and inhibited cell division with G2/M cell cycle arrest, leading to apoptotic cell death.

• Journal of Acupuncture Research
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• v.17 no.2
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• pp.169-186
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• 2000

To study anti-cancer effect and molecular biological mechanism of bee venom for aqua-acupuncture, the effects of bee venom on cell viability, apoptosis, and cell cycle were analyzed using MTT assay, tryphan blue assay, [3H]thymidine release assay, flow cytometric analysis, activity of caspase-3 protease activity assay, and immunocytometric analysis of PCNA. To explore whether anti-cancer effects of bee venom are associated with the transcriptional control of gene expression, quantitative RT-PCR analysis of apoptosis- and cell cycle-related genes was performed. The obtained results are summarized as follows: 1. The MTT assay demonstrated that cell viability was decreased by bee venom in a dose-dependant manner. 2. Significant induction of apoptosis was identified using tryphan blue assay, [$^3H$]thymidine release assay, and flow cytometric analysis of sub $G_1$ fraction. 3. In analysis of caspase-3 protease activity, the activity had increased significantly, in a dose-dependant manner. 4. Quantitative RT-PCR analysis of the apoptosis-related genes showed that Bcl-2 and $Bcl-X_L$ were down-regulated whereas Bax was up-regulated by bee venom treatment. 5. In flow cytometric analysis of cell cycle and immunocytometric analysis of PCNA expression, cell numbers of $G_1$ phase was increased by a dose-dependant manner. 6. In quantitative RT-PCR analysis of the cell cycle-related genes, p21, p27, and p57 were increased, while Cyclin D1, CDK4, c-Myc, c-Fos, and Histone H3 were decreased. In contrast, there were no remarkable changes in expression levels of CDC2 and c-Jun.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.1
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• pp.125-139
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• 2009

Purpose: This experiment was designed to find out increasing effects of S. barbata. co-treatment with anti-cancer drugs at cancer cell's growth inhibition effect. Methods: Divergent observational study of the S. barbata. co-treatment with Cisplatin treatment on HeLa cell. Cell viability using MTT assay, Cell Culture and Cytotoxicity Studies, Cell Cycle Analysis, Annexin V-FITC/PI assay, Cell morphological assessment, PARP cleavage using Western blotting analysis when HeLa cell were co-treated with Cisplatin and Scutellaria Barbata extracts. Results: When HeLa cell were co-treated with Cisplatin and Scutellaria Barbata extracts, we found out viability of HeLa cell, changing in the distribution of cell cycle, Annexin V-FITC staining, DAPI staining, PARP clavage protein assay by Western-blot. So Scutellaria Barbata extracts have increased apoptosis Conclusion: When co-treated Scutellaria Barbata extracts with anti-cancer drugs, the anti-cancer effects were increased. We still not sure which constituent apoptosis at cancer cells and activates anti-cancer effects suppressing, but we believe that it'll be revealed here after with following experiments.

• BMB Reports
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• v.46 no.2
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• pp.113-118
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• 2013

TTRAP is a multi-functional protein that is involved in multiple aspects of cellular functions including cell proliferation, apoptosis and the repair of DNA damage. Here, we demonstrated that the lentivirus-mediated overexpression of TTRAP significantly inhibited cell growth and induced apoptosis in osteosarcoma cells. The ectopic TTRAP suppressed the growth and colony formation capacity of two osteosarcoma cell lines, U2OS and Saos-2. Cell apoptosis was induced in U2OS cells and the cell cycle was arrested at G2/M phase in Saos-2 cells. Exogenous expression of TTRAP in serum-starved U2OS and Saos-2 cells induced an increase in caspase-3/-7 activity and a decrease in cyclin B1 expression. In comparison with wild-type TTRAP, mutations in the 5'-tyrosyl-DNA phosphodiesterase activity of TTRAP, in particular $TTRAP^{E152A}$, showed decreased inhibitory activity on cell growth. These results may aid in clarifying the physiological functions of TTRAP, especially its roles in the regulation of cell growth and tumorigenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10659-10663
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• 2015

Background: Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells. Materials and Methods: MCF-7 cells were plated at a density of $1{\times}10^5$ cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at $37^{\circ}C$, 5% $CO_2$ and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Results: Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The $IC_{50}$ value of rapamycin on the MCF-7 cells was determined as $0.4{\mu}g/ml$ (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. Conclusions: This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.399-402
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• 2012

Bufalin is a traditional oriental medicines which induces apoptosis in some lines of human tumor cells. It constitutes the major digoxin-like immunoreactive component of Chan Su, obtained from the skin and parotid venom glands of toads. Bufalin is cardioactive C-24 steroids that exhibits a variety of biological activities, such as cardiotonic, anaesthetic, blood pressure stimulatory, respiratory and antineoplastic effects. In terms of its anti-tumor activity, bufalin has been demonstrated to inhibit the growth of tumors, such as endometrial and ovarian cancers. This commentary introduces biologic and therapeutic effects of bufalin in treating some cancers. The compound is able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in human cancer cells.

• Biomedical Science Letters
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• v.23 no.3
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• pp.290-294
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• 2017

Metformin or sodium salicylate is known to induce apoptosis and G0/G1 phase arrest in a variety of cancer cells. However, the anti-cancer effects of the combined treatments for these drugs-induced apoptosis are yet unclear. Here, we found that the combined treatment of metformin and sodium salicylate increased the efficacy of chemotherapeutics against breast cancer cells. These combined drugs significantly inhibited cellular proliferation and induced apoptosis at an earlier stage in human MCF-7 breast cancer cells. Also, co-treatments of metformin and sodium salicylate induced G1 cell cycle arrest in MCF-7 cells more effectively than either agent alone. Taken together, these results demonstrate that dual metformin/sodium salicylate treatment prevents proliferation of MCF-7 cells by inducing apoptosis and G1 cell cycle arrest.