• BMB Reports
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• v.50 no.7
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• pp.361-366
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• 2017

Tetraploidy, a potential precursor of cancer-associated aneuploidy, is produced either by cell fusion or failure of cytokinesis. In this study, low p53-expressing HeLa cells were used to address the fate of cancer cells after fusion. We found that massive cell death or growth arrest occurred a few days after fusion. Interestingly, cells with larger nuclei preferentially died after fusion, suggesting that a larger deviation of DNA content is a strong inducer of apoptosis. Notably, a fraction of cells escaped cell death. Also, the stability of survivin increased, and its localization changed preferentially to the cytosol in fused cells. Knockdown of survivin decreased the survival of fused cells, more than observed in unfused cells, showing increased dependency of fused cells on survivin. Collectively, after cancer cell fusion, some fused cells avoid the apoptotic crisis partly owing to survivin, and continue to proliferate, a process that contributes to human cancer progression.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.89-89
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• 2020

In this study, we evaluated the effect of the extracts from Lonicera caerulea leaves (LCLE), branches (LCBE) and fruits (LCFE) on the cell growth and migration in human colorectal cancer cells, HCT116 and SW480 cells. LCLE and LCBE dose- and time-dependently inhibited the proliferation of HCT116 and SW480 cells. However, LCFE did not affect the proliferation of HCT116 and SW480 cells. In addition, LCLE and LCBE dramatically cell migration and wound healing in HCT116 cells. LCLE and LCBE decreased β-catenin protein level but not mRNA level in HCT116 and SW480 cells. Furthermore, LCLE decreased TCF4 level in both protein and mRNA level in HCT116 and SW480 cells. However, LCBE decreased TCF4 protein level but not mRNA level in HCT116 and SW480 cells. Based on these findings, LCLE and LCBE may inhibit the cell proliferation and migration through blocking Wnt signaling activation in human colorectal cancer cells. Therefore, LCLE and LCBE may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.137-137
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• 2002

Capsaicin has been reported to induce apoptosis in various cancer cells. However, its effect on bladder cancer cells has not been studied. In this study, we investigated whether capsaicin induces apoptosis in murine orthotopic bladder cancer MBT-2 cells and reactive oxydative species(ROS) are involved in capsaicin-induced apoptotic process.(omitted)

• Molecules and Cells
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• v.25 no.1
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• pp.119-123
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• 2008

Pyrimidine antagonists including 5-Fluorouracil (5-FU) have been used in chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a mainstay treatment for colorectal cancer. It is a pro-drug that is converted to the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5-FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One of the major obstacles to successful chemotherapy is the resistance of cancer cells to anti-cancer drugs. Therefore, it is important to elucidate resistance mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a model system to investigate the mechanism of resistance to 5-FU, which induces germ cell death and inhibits larval development in C. elegans. We screened 5-FU resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants out of 72,000 F1 individuals screened, and mapped them into three complementation groups. We propose that C. elegans could be a useful model system for studying mechanisms of resistance to anti-cancer drugs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3629-3633
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• 2015

Cancer stem cells (CSCs) are rare subpopulations within tumors which are recognized as culprits in cancer recurrence, drug resistance and metastasis. However, the molecular mechanisms of how CSCs are regulated remain elusive. Kr$\ddot{u}$ppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse functions in cell differentiation, proliferation, embryogenesis and pluripotency. Recent progress has highlighted the significance of KLFs, especially KLF4, in cancer and CSCs. Therefore, for better therapeutics of cancer disease, it is crucial to develop a deeper understanding of the mechanisms of how KLF4 regulate CSC functions. Herein we summarized the current understanding of the transcriptional regulation of K LF4 in CSCs, and discussed the functional implications of targeting CSCs for potential cancer therapeutics.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2637-2641
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• 2013

6,8-Dihydroxy-7-methoxy-1-methyl-azafluorenone (DMMA), a purified compound from Polyalthia cerasoides roots, is cytotoxic to various cancer cell lines. The aims of this study were to demonstrate the type of cancer cell death and the mechanism(s) involved. DMMA inhibited cell growth and induced apoptotic death in human leukemic cells (HL-60, U937, MOLT-4), human breast cancer MDA-MB231 cells and human hepatocellular carcinoma HepG2 cells in a dose dependent manner, with $IC_{50}$ values ranging between 20-55 ${\mu}M$. DMMA also decreased cell viability of human peripheral blood mononuclear cells. The morphology of cancer cells induced by the compound after staining with propidium iodide and examined under a fluorescence microscope was condensed nuclei and apoptotic bodies. Mitochondrial transmembrane potential (MTP) was decreased after 24h exposure in all five types of cancer cells. DMMA-induced caspase-3, -8, and -9 activity was strongly induced in human leukemic HL-60 and MOLT-4 cells, while in U937-, MDA-MB231- and HepG2-treated cells there was partial induction of caspase. In conclusion, DMMA-induced activation of caspase-8 and -9 resulted in execution of apoptotic cell death in human leukemic HL-60 and MOLT-4 cell lines via extrinsic and intrinsic pathways.

• Herbal Formula Science
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• v.23 no.1
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• pp.101-110
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• 2015

Objectives : The purpose of this study was to investigate the anti-cancer effects of Oldenlandia diffusa extract on WiDr human colorectal adenocarcinoma cells. Methods : We examined cell death by (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) MTT assay and the caspase 3 and 9 activity assay with Oldenlandia diffusa extract. To examine the inhibitory effects of Oldenlandia diffusa extract, we performed a cell cycle (sub-G1) analysis and mitochondrial membrane potential for the WiDr cells after 24 hours with Oldenlandia diffusa extract. Results : 1. Oldenlandia diffusa extract induced cell death in WiDr cells. 2. The sub-G1 peak was increased by Oldenlandia diffusa extract in WiDr cells. 3. Oldenlandia diffusa extract leads to increase the mitochondrial membrane depolarization in WiDr cells. 4. Oldenlandia diffusa extract increases caspase 3 and 9 activities in WiDr cells. 5. Oldenlandia diffusa extract combined with several anti-cancer drugs (paclitaxel, 5-fluorouracil, cisplatin, ectoposide, doxorubicin and docetaxel) markedly inhibited the growth of WiDr cells compared to Oldenlandia diffusa extract and anti-cancer drugs alone. Conclusions : Oldenlandia diffusa extract has an apoptotic role in human colorectal cancer cells and a potential role in developing therapeutic agents against colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5703-5707
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• 2015

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of their antioxidative properties. Melissa officinalis L. (MO), an aromatic and medicinal plant, is well known in thios context. However, toxicity against cancer cells has not been fully studied. Here, we investigated the selective anticancer effects of an MO extract (MOE) in different human cancer cells. Materials and Methods: a hydro-alcoholic extract of MO was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. MTT assays were used to evaluate cytotoxicity of different doses of MOE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer cells), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, MOE reduced the cell viability to values below 33%, even at the lowest doses. In all cases, $IC_{50}$ values were below $5{\mu}g/ml$. The mean growth inhibition was 73.1%, 86.7%, 79.9% and 77.8% in SKOV3, MCF-7 and PC-3 and A549 cells, respectively. Conclusions: Our results indicate that a hydro-alcoholic extract of MO possess a high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important than a maximally tolerated one. Moreover, the antiprolifreative effect of MO seems to be tumor type specific, as hormone dependant cancers were more sensitive to antitumoral effects of MOE.

• Molecules and Cells
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• v.37 no.9
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• pp.699-704
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• 2014

Themetastasis-associated gene 1 (MTA1) oncogene hasbeen suggested to be involved in the regulation of cancer progression. However, there is still no direct evidence that MTA1 regulates cisplatin (CDDP) resistance, as well as cancer stem cell properties. In this study, we found that MTA1 was enriched in CNE1/CDDP cells. Knock down of MTA1 in CNE1/CDDP cells reversed CSCs properties and CDDP resistance. However, ectopic expression of MTA1 in CNE1 cells induced CSCs phenotypes and CDDP insensitivity. Interestingly, ectopic overexpression of MTA1-induced CSCs properties and CDDP resistance were reversed in CNE1 cells after inhibition of PI3K/Akt by LY294002. In addition, MTA1 expression and Akt activity in CNE1/CDDP cells was much higher than that in CNE1 cells. These results suggested that MTA1 may play a critical role in promoting CDDP resistance in NPC cells by regulatingcancer stem cell properties via thePI3K/Akt signaling pathway. Our findings suggested that MTA1 may be a potential target for overcoming CDDP resistance in NPC therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.627-633
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• 2015

Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.