• Toxicological Research
• /
• v.20 no.4
• /
• pp.307-313
• /
• 2004

The present study was undertaken to investigate the effects of mistletoe (Viscum album var. coloratum) growing on Carpinus laxiflora BL. on proliferation and differentiation of HL-60 acute promyelocytic leukemia cells. Aqueous extract and its $(NH_2)_2SO_4$ saturated fractions of the mistletoe exhibited potent anti-proliferation activity against HL-60 cells. Moreover, when HL-60 cells were treated with 0~30% and 30～70% $(NH_2)_2SO_4$ saturated fractions of the mistletoe, HL-60 expressed CD 66b or CD 14 cell surface antigens and showed activity to reduce nitroblue tetrazolium, indicating that mistletoe induces the differentiation of HL-60 into granulocytes or monocytes. To understand how mistletoe induces the differentiation, we investigated the expression of molecules for modulating the proliferation and differentiation of leukemia cells, such as c-Myc and myeloblastin. The 0~30% $(NH_2)_2SO_4$ saturated fraction of the mistletoe reduced the mRNA levels of c-Myc and myeloblastin in a time-dependent manner. The results indicate that the mistletoe induces the differentiation of HL-60 cells via the decrease of c-Myc and myeloblastin expressions. Thus, it is suggested that mistletoe has a therapeutic potential for the treatment of acute promyelocytic leukemia.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.20
• /
• pp.8829-8836
• /
• 2014

Background: Cyclooxygenase-2 (COX-2), considered to have tumor-promoting potential, is highly expressed in a variety of tumors, including breast cancer. Since the functions and action mechanisms of COX-2 in breast cancer have not been fully elucidated, in the present study, the effects of target inhibiting COX-2 with recombinant adenovirus Ad-COX-2-shRNA on malignant biological behavior were investigated in representative cell lines. Materials and Methods: Breast cancer MDA-MB-231 and MCF-7 cells were transfected with Ad-COX-2-shRNA and COX-2 expression was tested by RT-PCR and Western blotting. Changes in proliferation, apoptosis and invasion of breast cancer cells were detected with various assays including MTT, colony forming, flowcytometry and Transwell invasion tests. The expression of related proteins involved in the cell cycle, apoptosis, invasion and signaling pathways was assessed by Western blotting. Results: COX-2 expression was significantly reduced in both breast cancer cell lines infected with Ad-COX-2-shRNA, with obvious inhibition of proliferation, colony forming rate, G2/M phase passage and invasion, as well as induction of apoptosis, in MDA-MB-231 and MCF-7 cells, respectively. At the same time, proteins related to the cell cycle, anti-apoptosis and invasion were significantly downregulated. In addition, c-myc expression and phosphorylation activation of Wnt/${\beta}$-catenin and p38MAPK pathways were reduced by the Ad-COX-2-shRNA. Conclusions: COX-2 expression is associated with proliferation, apoptosis and invasion of breast cancer cells, and its mechanisms of action involve regulating expression of c-myc through the p38MAPK and Wnt/${\beta}$-catenin pathways.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.6
• /
• pp.1441-1447
• /
• 2003

The purpose of this research was to investigate the effects of Chungjokupye-tang(CJKPT) on the anti-carcinogenic action. The cell viability of mouse spienocytes and thymocytes were enhanced by the addition of CJKPT. CJKPT were increased of splenic and thymic T lymphocytes, such as T/sub H/ cells were markedly increased by the treatment of CJKPT in vivo. CJKPT treatment induced the apoptotic cell death of Jurkat and HL60 leukemia cells. CJKPT reduced mitochondrial transmembrane potential and increased the expression of ICE, c-myc and p53 gene in Molt-4cells dose dependant manner. These results suggest that CJKPT have an anti-carcinogenic action via immunoregulatory mechanism.

• Microbiology and Biotechnology Letters
• /
• v.22 no.4
• /
• pp.347-352
• /
• 1994

Cytotoxic test was performed by SRB assay on human epidermoid carcinoma HEp-2 cell line for screening the soil microorganism, secreting anticancer agent. One microorganism was selected among two thousand microorganisms for its highest cytotoxicity. And this microorganism was identified with Streptomyces species after performing of diaminopimeric acid and reducing sugar analysis of cell wall and analysing the cultural characteristics and named Streptomyces sp. SM 1119. The effect of anticancer agent in SM 1119 culture extract on the cell cycle was studied by using GG$_{o}$ synchronized NIH 3T3 cells. The extract inhibited the serum stimulation of GG$_{o}$ NIH 3T3 cell only within 1 hour after serum stimulation but not after 6 hours. The extract also reduced the amount of c-myc mRNA in Colo 320 cell. These results suggest that the anticancer agent in the extract inhibits the progression of cell cycle very early stages, probably from G$_{0}$ to G$_{1}$.

• BMB Reports
• /
• v.29 no.1
• /
• pp.68-72
• /
• 1996

Ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), secondary bile acids, have been shown to have a cell differentiation activity in mouse F9 teratocarcinoma stem cells. Treatment with bile acids induced morphological changes, including cytoplasmic and nuclear membrane blebbing, aggregation of organelles, and chromatin condensation, corresponding to apoptosis. Moreover, the bile acids induced intemucleosomal DNA fragmentation, a hallmark of apoptosis. In addition, the expression of c-jun was increased, but that of c-myc and laminin was decreased during apoptosis induced by the bile acids in F9 cells. These results suggest that the bile acids can induce apoptosis in F9 cells. Furthermore, the c-jun expression may be related to the apoptosis induced by UDCA or LCA in F9 cells.

• Biomolecules & Therapeutics
• /
• v.17 no.4
• /
• pp.370-378
• /
• 2009

N-myc downstream-regulated gene 2 (NDRG2) has recently been found to be a tumor suppressor gene. Although it has been reported that NDRG2 expression in breast cancer cells decreases cell proliferation by inhibiting STAT3 activation via SOCS1 induction, the molecular mechanism of chemotherapeutic agent-induced apoptosis is not well known. To elucidate the effect of NDRG2 on the apoptotic pathway induced by doxorubicin, we established stable cell lines expressing NDRG2 and investigated the effect of NDRG2 expression on the doxorubicin-induced apoptosis. While STAT3 activation was remarkably inhibited by NDRG2 overexpression, the expression level of p21 was increased by NDRG2 expression. We confirmed that NDRG2-expressing cells treated with doxorubicin suppressed STAT3 activation and upregulated p21 expression. NDRG2 expression considerably enhanced TUNEL positive apoptotic cells, poly-ADP ribose polymerase (PARP) cleavage, release of cytochrome c to cytosol, and caspase-3 activity in doxorubicin-induced apoptosis. Bid expression in a resting state and after treatment with doxorubicin increased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells. Meanwhile, Bcl-$x_L$ expression decreased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells in a resting state and in doxorubicin-treated cells. Collectively, these data suggest that suppression of STAT3 activation by NDRG2 influences the sensitivity to doxorubicin-induced apoptosis of breast cancer cells and this may provide a potential therapeutic benefit to overcome the resistance against doxorubicin in breast cancer.

• YAKHAK HOEJI
• /
• v.36 no.6
• /
• pp.529-537
• /
• 1992

To investigate the effect of ursolic acid on the expression of oncogenes in tumor cells of mice, sarcoma 180 ascites tumor cells were implanted into the left groin of ICR mice and the tumor bearing mice were treated with ursolic acid. The expression of oncogenes were measured by in situ hybridization method. Ursolic acid significantly reduced the expression of oncogenes in the tumor cells. Therefore, it can be said that the prestated anticarcinogenic effect of ursolic acid could be partly ascribed to the mechanism included in the oncogene´s transcription level.

• Biomolecules & Therapeutics
• /
• v.26 no.5
• /
• pp.464-473
• /
• 2018

Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1. Notably, treatment with an anti-GRP78 antibody blocked these effects. In addition, pretreatment with STAT3 short interfering RNA (siRNA) inhibited the increase in p-JAK2, c-Myc, cyclin D1, and BCL3 levels caused by Cripto and attenuated the pro-survival action of Cripto on MSCs. We also found that incubation with Cripto protected MSCs from apoptosis caused by hypoxia or $H_2O_2$ exposure, and the level of caspase-3 decreased by the Cripto-induced expression of B-cell lymphoma 3-encoded protein (BCL3). These effects were sensitive to down-regulation of BCL3 expression by BCL3 siRNA. Finally, we showed that Cripto enhanced expression levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). In summary, our results demonstrated that Cripto activated a novel biochemical cascade that potentiated MSC proliferation and survival. This cascade relied on phosphorylation of JAK2 and STAT3 and was regulated by GRP78. Our findings may facilitate clinical applications of MSCs, as these cells may benefit from positive effects of Cripto on their survival and biological properties.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.12
• /
• pp.5189-5193
• /
• 2016

Objective: Dorema glabrum Fisch. & C.A. Mey is a perennial plant that has several curative properties. Anti-proliferative activity of seeds of this plant has been demonstrated in a mouse fibrosarcoma cell line. The aim of the present study was to evaluate cytotoxicity of D. glabrum root extracts in a human gastric adenocarcinoma (AGS) cell line and explore mechanisms of apoptosis induction, cell cycle arrest and altered gene expression in cancer cells. Materials and Methods: The MTT assay was used to evaluate IC50 values, EB/AO staining to analyze the mode of cell death, and flow cytometry to assess the cell cycle. Quantitative real-time polymerase chain reaction (qRT-PCR) amplification was performed with apoptosis and cell cycle-related gene primers, for cyclin D1, c-myc, survivin, VEGF, Bcl-2, Bax, and caspase-3 to determine alteration of gene expression. Results: Our results showed that n-hexane and chloroform extracts had greatest toxic effects on gastric cancer cells with IC50 values of $6.4{\mu}g/ml$ and $4.6{\mu}g/ml$, respectively, after 72 h. Cell cycle analysis revealed that the population of treated cells in the G1 phase was increased in comparison to controls. Cellular morphological changes indicated induction of apoptosis. In addition, mRNA expression levels of Bax and caspase-3 were increased, and of bcl-2 survivin, VEGF, c-myc and cyclin D1 were decreased. Conclusion: Our study results suggest that D. glabrum has cytotoxic effects on AGS cells, characterized by enhanced apoptosis, reduced cell viability and arrest of cell cycling.

• Proceedings of the Korean Society of Developmental Biology Conference
• /
• 2003.10a
• /
• pp.70-70
• /
• 2003

The uterus undergoes dynamic changes during the cycle and displays many features typical of developmental process. In order to be prepared for implantation, endometrium undergoes predictable, sequential phases of proliferation and secretory changes. The uterus during estrus cycle synthesize a complex of signaling molecules with specific spatial and temporal modes of expression and which are critical for cell proliferation and differentiation. The purpose of this investigation was to use cDNA microarrays to evaluate the expression of genes of rat uterus in estrus cycle. Animals were sacrificed on proestrus, estrus, metestrus, diestrus. Differential gene expression profiles were revealed(growth-related c-myc reponsive protein RCL, heat shock 47-kDa protein (HSP47), cytochrome c oxidase polypeptide Vlc2 (COX6C2), calreticulin (CALR)). Reverse transcription polymerase chain reaction (RT-PCR) was used to validate the relative expression pattern. Using this approach, we found several genes whose expression in rat uterus was altered with estrus cycle. Our long-term goal is to determine the role of these differentially expressed genes during estrus cycle. This study was supported by through the Biohealth Products Research Center(BPRC), Inje University.