• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.157-164
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• 2003

Cervi Parvum Cornu(CPC) is that the young horn of deer family and has been traditionally used as a medicine in Eastern. The purpose of present study was to investigate the effects of CPC on cell cycle progression and its molecular mechanism in human periodontal ligament cells (HPOLC). In cell proliferation assay, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1 ㎍/ml and 10 ㎍/ml of CPC were used, all treatment groups increased the cell growth. Maximal cell proliferation was observed in cells exposed to 100 ng/ml of CPC at 4 day, and 10 ng/ml and 100 ng/ml of CPC at 6 days. S phase was increased and G1 phase was decreased in the group treated with 100 ng/ml of CPC in cell cycle analysis. The protein levels of cyclin D1 were not changed, but the levels of cyclin E, cdk 2, cdk 4 and cdk 6 were increased. The protein levels of p21, pRb were decreased as compared to that of control group, but the levels of p53 was not changed in the cells both treated with CPC Md untreated. These results suggested that CPC increases the cell proliferation and cell cycle progression in HPDLC, which is linked to an increased cellular levels of cyclin E, cdk 2, cdk 4 and cdk 6, and decreased the levels of p53, p21.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.95-101
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• 2007

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a naturally occurring phytoallexin abundant in grapes and several plants, has been shown to be active in inhibiting proliferation and inducing apoptosis in several human cancer cell lines. On the line of the biological activity of resveratrol, a variety of resveratrol analogs were synthesized and evaluated for their growth inhibitory effects against several human cancer cell lines. In the present study, we found that one of the resveratrol analogs, 3,4,5-trimethoxy-4’-bromo-cis-stilbene, markedly suppressed human colon cancer cell proliferation (EC$_{50}$ = 0.01 ${\mu}$g/ml), and the inhibitory activity was superior to its corresponding trans-isomer (EC$_{50}$ = 1.6 ${\mu}$g/ml) and resveratrol (EC$_{50}$ = 18.7 ${\mu}$g/ml). Prompted by the strong growth inhibitory activity in cultured human colon cancer cells (Col2), we investigated its mechanism of action. 3,4,5-Trimethoxy-4’-bromo-cis-stilbene induced arrest of cell cycle progression at G2/M phase and increased at sub-G1 phase DNA contents of the cell cycle in a time- and dose-dependent manner. Colony formation was also inhibited in a dose-dependent manner, indicating the inhibitory activity of the compound on cell proliferation. Moreover, the morphological changes and condensation of the cellular DNA by the treatment of the compound were well correlated with the induction of apoptosis. These data suggest the potential of 3,4,5-trimethoxy-4’-bromo-cis-stilbene might serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and inducing apoptosis for the human colon cancer cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.90-90
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47D and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.2
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• pp.154-163
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• 2000

Growth factors and the receptors play an important role in the regulation of the growth and development of mammalian cells. In particular, epidermal growth factor is a polypeptide with potent mitogenic activity that stimulates proliferation of various normal and neoplastic cells through the interaction with its specific receptor(EGFR). EGFR has been described as a parameter of poor prognosis in many human neoplasms such as breast, bladder, and vulvar cancers. The objectives of this study are the evaluation of the expression of EGFR and cell cycle analysis in the head and neck squamous cell carcinomas(SCC), and the evaluation of the correlation between clinico-patholgic features and expression of EGFR and S-phase fraction. 37 head and neck squamous cell carcinoma specimens were evaluated for expression of EGFR by Western blot analysis and S-phase fraction by cell cycle analysis using the flow cytometry. The obtained results were as follows : 1. The expressions of EGFR were observed in 20 specimens(54%) among 37 head and neck SCC specimens. In case of oral SCC, 15 specimens(56%) out of 27 specimens were observed, and in case of nasopharyngeal SCC 5 specimens(50%) out of 10 specimens. 2. There was no correlation between clinical features(location, stage) of head and neck SCC and expression of EGFR (p>0.05). 3. There was a significant correlation between histo-pathological differentiation of head and neck SCC and expression of EGFR (p<0.02). 4. There was a significant correlation between expression of EGFR and S-phase fraction of cell cycle in the head and neck SCC (p<0.05). The above results suggest that expression of EGFR and S-phase fraction of cell cycle are adjunctive prognostic marker in the head and neck squamous cell carcinomas.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.180-180
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER Positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47B and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.2
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• pp.186-198
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• 2006

Purpose : The purpose of this study is to demonstrate the direct inhibitory effect of Hyulbuchukeotang on the proliferation of uterine leiomyoma cells through an experiment treating uterine leiomyoma cells cultivated by explantation with indicated concentrations of Hyulbuchukeotang and to research the gene expression related to cell cycle ill order to discover the connection with apoptosis and its mechanism by analyzing cell cycle. Methods : After primary culture of uterine leiomyoma cells, the cultivated uterine leiomyoma cells were treated with indicated concentrations of Hyulbuchukeotang for 24 hours. The inhibitory effect on the cell proliferation was determined by the cell count assay. The value of a cell count assay represent the percentage of cells in a phase of the cell cycle compared with total cells. In addition, a link between Hyulbuchukeotang and apoptosis was examined through flow cytometric analysis by FACS and DNA fragmentation analysis. Finally, the degree of gene expression related to cell cycle was evaluated by Western blot analysis. Results : The inhibitory effect of Hyulbuchukeotang increase of uterine leiomyoma cells treated with indicated concentrations of Hyulbuchkeotang increases. The result of gene expression related to G1 phase after treating with 100, 250, 500, 1,000 ${\mu}g/ml$ concentrations of Hyulbuchukeotang. on uterine leiomyoma cells is that the gene expression of p27 was increased but that of p53 an p21 remained unchanged and the gene of pRB, pro-caspase 3 was decreased. Conclusion Through the mentioned experiments, it is demonstrated that Hyulbuchkeotang is effective in inhibiting Proliferation of uterine leiomyoma cells by extending cell cycle G1. However it is not considered that the inhibitory effect results from the aptoposis.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.8.1-8.12
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• 2018

FAM46B is a member of the family with sequence similarity 46. Little is known about the expression and functional role (s) of FAM46B in prostate cancer (PC). In this study, the expression of FAM46B expression in The Cancer Genome Atlas, GSE55945, and an independent hospital database was measured by bioinformatics and real-time PCR analysis. After PC cells were transfected with siRNA or a recombinant vector in the absence or presence of a ${\beta}$-catenin signaling inhibitor (XAV-939), the expression levels of FAM46B, C-myc, Cyclin D1, and ${\beta}$-catenin were measured by western blot and realtime PCR. Cell cycle progression and cell proliferation were measured by flow cytometry and the CCK-8 assay. The effects of FAM46B on tumor growth and protein expression in nude mice with PC tumor xenografts were also measured. Our results showed that FAM46B was downregulated but that ${\beta}$-catenin was upregulated in patients with PC. FAM46B silencing promoted cell proliferation and cell cycle progression in PC, which were abrogated by XAV-939. Moreover, FAM46B overexpression inhibited PC cell cycle progression and cell proliferation in vitro and tumor growth in vivo. FAM46B silencing promoted ${\beta}$-catenin protein expression through the inhibition of ${\beta}$-catenin ubiquitination. Our data clearly show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of ${\beta}$-catenin.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.151-161
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• 2022

This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.

• Journal of Microbiology and Biotechnology
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• v.13 no.2
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• pp.217-224
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• 2003

Previously, we developed a CHO cell line (CHO-OTC1-Al9) that expresses the first two enzymes in the urea cycle and exhibits a higher ammonia-removing ability and faster growth rate than a vector-controlled CHO cell line (CHO-neo-5). The current study was undertaken to develop a cell line with an ammonia-removing ability higher than the cell line developed previously. To accomplish this, CHO cell lines expressing the first three, first four, or all five enzymes of the urea cycle were constructed using a stable transfection method. Finally, the CHO-AS-16, CHO-AL-19, and CHO-Arg-11 cell lines expressing the first three, first four, and all five enzymes of the urea cycle, respectively, were selected and found to exhibit higher ammonia-removing ability than the CHO-OTC1-Al9 cell line. Among the three selected cell lines, CHO-AL-19 showed the highest ammonia-removing ability and highest cell viability at a higher cell density, with 40% and 15% lower ammonia concentration in the, culture media than that of CHO-neo-5 and CHO-OTC1-A19 cell lines, respectively. CHO-AL-19 also showed 44% and 10% higher cell viability than the CHO-neo-5 and CHO-OTC-Al9 cell lines, at a higher cell density, respectively. The ammonia concentrations in the culture media were expressed as the ammonia concentration/cell, and the CHO-AL-19 cells revealed 45-60% and 20% lower ammonia concentration/cell than the CHO-neo-5 and CHO-OTC1-Al9 cells, respectively.

• Journal of Periodontal and Implant Science
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• v.33 no.3
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• pp.415-437
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• 2003

Ginseng Radix(GR) had been used widely from oriental medicine and the effects of it have been investigated by many researchers. The purpose of present study was to investigate the effects of GR on the cell cycle progression and its molecular mechanism in human fetal osteoblast. The results were as follows. Increased cell proliferation was observed in cells exposed to 100 ng/ml, 10 ng/ml of GR-1 at 12 hours and 24 hours, 1 ${\mu}g$/ml of GR-1 at 48 hours, and 100 ${\mu}g$/ml, 10 ${\mu}g$/ml of GK-2 at 12 hours, all treatment groups of GR-2 at 24 hours(p<0.05). S phase and G1 phase was increased in the group of treated with 100 ng/ml of GR-1, with 10 ${\mu}g$/ml and 1 ${\mu}g$/ml of GR-2, with 100 ${\mu}g$/ ml and 10 ${\mu}g$/ml of GR-3 in the cell cycle analysis. The cell cycle regulation protein levels of Cyclin D1, Cyclin E, CDK 2. CDK 4 and CDK 6 were increased in the group of treated with 1 ${\mu}g$/ml and 100 ng/ml of GR-1, with 10 ${\mu}g$/ml and 1 ${\mu}g$/ml of GR-2, with 100 ${\mu}g$/ ml and 10 ${\mu}g$/ml of GR-3. On the other hand, p21 was decreased in the treatment group with 1 ${\mu}g$/ml and 100 ng/ml of GR-1, with 10 ${\mu}g$/ml and 1 ${\mu}g$/ml of GR-2, 10 ${\mu}g$/ml of GR-3, and p53 and p16 was decreased in the treatment group with 100 ng/ml of GR-1, 100 ${\mu}g$/ml and GR-3 and pRb was decreased in the all treatment groups except 1 ${\mu}g$/ml of GR-1. These results suggested that GR increases the cell proliferation and the cell cycle progression in human fetal osteoblast, which is linked to increased cell cycle regulation protein levels of Cyclin D1 , Cyclin E, CDK 2, CDK 4, CDK 6 and decreased cell cycle regulation protein levels of p21, pRb.