• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3559-3567
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• 2016

Background: In recent years, there has been considerable research on recycling of agro-industrial waste for production of bioactive compounds. The food processing industry produces large amounts of citrus peels that may be an inexpensive source of useful agents. Objective: The present work aimed to explore the phytochemical content, antioxidant, anticancer, antiproliferation, and antigenotxic activities of lemon, grapefruit, and mandarin peels. Materials and Methods: Peels were extracted using 98% ethanol and the three crude extracts were assessed for their total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant activity using DPPH (1, 1-diphenyl-2-picrylhydrazyl). Their cytotoxic and mitogenic proliferation activities were also studied in human leukemia HL-60 cells and mouse splenocytes by CCK-8 assay. In addition, genotoxic/antigenotoxic activity was explored in mouse splenocytes using chromosomal aberrations (CAs) assay. Results: Lemon peels had the highest of TPC followed by grapefruit and mandarin. In contrast, mandarin peels contained the highest of TFC followed by lemon and grapefruit peels. Among the extracts, lemon peel possessed the strongest antioxidant activity as indicated by the highest DPPH radical scavenging, the lowest effective concentration 50% ($EC_{50}=42.97{\mu}g\;extract/mL$), and the highest Trolox equivalent antioxidant capacity (TEAC=0.157). Mandarin peel exhibited moderate cytotoxic activity ($IC_{50}=77.8{\mu}g/mL$) against HL-60 cells, whereas grapefruit and lemon peels were ineffective anti-leukemia. Further, citrus peels possessed immunostimulation activity via augmentation of proliferation of mouse splenocytes (T-lymphocytes). Citrus extracts exerted non-cytotoxic, and antigenotoxic activities through remarkable reduction of CAs induced by cisplatin in mouse splenocytes for 24 h. Conclusions: The phytochemical constituents of the citrus peels may exert biological activities including anticancer, immunostimulation and antigenotoxic potential.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권2호
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권5호
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• pp.396-402
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• 2011

Introduction: Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids with potent mitogenic activity that stimulates the proliferation of a range of normal and neoplastic cells through an interaction with its specific receptor (epidermal growth factor receptor, EGFR). This interaction plays a key role in tumor progression including the induction of tumor cell proliferation. An increased EGFR copy number have been associated with a favorable response to EGFR tyrosine kinase inhibitors therapy. In contrast, K-ras mutations tend to predict a poor response to such therapy. The aim of this study was to determine the correlation between the clinicopathological factors and the up-regulation of EGFR expression and Kras mutations in oral squamous cell carcinoma. Materials and Methods: This study examined the immunohistochemical staining of EGFR, K-ras mutation detection with peptide nucleic acid (PNA)-based real-time polymerase chain reaction (PCR) clamping in 20 specimens from 20 patients with oral squamous cell carcinoma. Results: 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, a high level of EGFR staining was observed. The correlation between immunohistochemical EGFR expression and histological differentiation, as well as the tumor size of the specimens was significant (Pearson correlation analysis, significance [r] >0.5, P<0.05). 2. In PNA-based real-time PCR clamping analysis, a K-ras mutation was not detected in all specimens. Conclusion: These findings suggest that the up-regulation of the EGFR may play a role in the progression and invasion of oral squamous cell carcinoma that is, independent of a K-ras mutation.

• BMB Reports
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• 제41권5호
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• pp.369-375
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• 2008

Polygonatum cyrtonema Lectin (PCL), which is classified as a monocot mannose-binding lectin, has received great regards for its uniquely biological activities and potentially medical applications in cancer cells. This paper was initially aimed to study apoptosis of PCL on Hela cells. Thus, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method was carried out. Through observation of cell morphologic changes and Lactate dehydrogenase (LDH) activity-based cytotoxicity assays, PCL induced HeLa cell apoptosis in a dose-dependent manner. To further gain structural basis, multiple alignments, homology modeling and docking experiments were performed to analyze the correlation between its biological activities and mannose-binding sites. Eventually, considering docking data, chemical modification properties on the three mannose-binding sites were analyzed by a series of biological experiments (e.g., hemagglutinating and mitogenic activity assays, fluorescence and Circular Dichrosim (CD) spectroscopy) to profoundly identify the role of some key amino acids in the structure-function relationship of PCL.

• KSBB Journal
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• 제25권1호
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• pp.47-54
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• 2010

The mycelial dispersed growth of Cordyceps sinensis was optimized in submerged batch culture at initial pH of 5.0, 150 rpm, and $25^{\circ}C$. The morphological data showed much more dispersed growth of C. sinenesis at initial pH of 5.0. Also, projected area, main hyphal length and number of tips for the mycelial growth of initial pH 5.0 were higher than those of other initial pHs. The industrial medium for mycelial production of C. sinensis was determined to be molasses of 100 g and crushed brewery yeast of 10 g per liter as carbon and nitrogen sources, respectively. With these culture conditions, the maximum production of mycelia was approximately 30.0 g per liter by batch culture in 5-liter jar fermenter with no controlled pH. This result suggests that large-scale mycelia production of C. sinensis may be possible in submerged batch culture. The hot water extract of mycelia from C. sinensis was mainly composed of 83.0% carbohydrate, 11.8% protein, 1.9% lipid, and 2.4% ash and there were present glucose, mannose, galactose, and arabinose as molar ratio of 8.79 : 2.59 : 1.34 : 1.0 in the carbohydrate, respectively. In the experiment using spleen cell and macrophage, the extract showed potent mitogenic and immuno-stimulating activities and among various components, an important factor that contribute to the immunological activities was turned out to be carbohydrate moiety.

• 대한수의학회지
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• 제36권3호
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• pp.647-655
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• 1996

To establish the effective ways to prevent bovine mastitis, the study has been performed to investigate the attributable factors causing down-regulation of immune responses in mammary gland of non-lactating cows. Lymphocytes from peripheral blood and mammary gland secretions(MGS) were obtained from normal healthy cows and mastitic cows, respectively. Lymphoblastogenesis were investigated carefully by adding different concentrations of supernatants collected from pure-cultures of neutrophils seperated from peripheral blood and MGS, respectively. The results obtained are as follows ; 1. Lymphoblastogenesis activity stimulated by Con A, PWM and PHA were significantly reduced in MGS from mastitic cows. 2. Supernatants collected from pure-culture of neutrophils separated both from peripheral blood and MGS showed inhibitory effect on mitogenic lymphoblastogenesis. 3. Supernatants from mammary gland neutrophils have shown 7 times more inhibitory activity than those from peripheral blood and this inhibitory effect was increased in proportion to increasing concentrations of supernatants when those were added to lymphoblast cells in culture.

• Molecules and Cells
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• 제28권1호
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• pp.67-71
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• 2009

Estrogen receptor ${\alpha}$ ($ER{\alpha}$) mediates the mitogenic effects of estrogen. $ER{\alpha}$ signaling regulates the normal growth and differentiation of mammary tissue, but uncontrolled $ER{\alpha}$ activation increases the risk to breast cancer. Estrogen binding induces ligand-dependent $ER{\alpha}$ activation, thereby facilitating $ER{\alpha}$ dimerization, promoter binding and coactivator recruitment. $ER{\alpha}$ can also be activated in a ligand-independent manner by many signaling pathways, including protein kinase A (PKA) signaling. However, in several $ER{\alpha}$-positive breast cancer cells, PKA inhibits estrogen-dependent cell growth. FoxH1 represses the transcriptional activities of estrogen receptors and androgen receptors (AR). Interestingly, FoxH1 has been found to inhibit the PKA-induced and ligand-induced activation of AR. In the present study, we examined the effects of PKA activation on the ability of FoxH1 to represses $ER{\alpha}$ transcriptional activity. We found that PKA increases the protein stability of FoxH1, and that FoxH1 inhibits PKA-induced and estradiol-induced activation of an estrogen response element (ERE). Furthermore, in MCF7 cells, FoxH1 knockdown increased the PKA-induced and estradiol-induced activation of the ERE. These results suggest that PKA can negatively regulate $ER{\alpha}$, at least in part, through FoxH1.

• 동의생리병리학회지
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• 제21권2호
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• pp.485-490
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• 2007

Zingiberis rhizoma(ZB) has been used to treat a various condition and disease in many traditional preparation. The present study was conducted to investigate the immunomodulatory effect on cyclophosphamide(CY)-induced immunotoxicity of aqueous-extracted ZB(ZBE) using in vitro and in vivo experiment. In vitro experiment, the mouse spleen cells proliferation and nitric oxide(NO) production in RAW 264.7 mouse macrophage cells were investigated. ZBE enhanced mitogenic activity in mouse spleen cells. The suppression of CY-induced mouse speen cell proliferation was significantly restored by ZBE treatment. ZBE inhibited NO production, iNOS mRNA and protein levels in LPS-stimulated RAW 264.7 cells. In vivo experiment, ZBE was orally administrated(single dose of 150mg/kg for 12 days) and CY i.p(150mg/kg) injected to SD rats. In CY alone injected group, body weights and spleen weights, and a various hematological parameters were reduced when compared with control group, whereas those values were increased by concomitant treatment of CY and ZBE when compared with CY alone injected group. These results indicated that ZBE can modulate CY-induced immune suppression through immune cell proliferation, the regulation of NO production and the inhibition of CY-induced immunotoxicity.

• 동의생리병리학회지
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• 제21권2호
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• pp.414-424
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• 2007

Adenophorae Radix (AR), Liriopis Tuber (LT), Dendrobii Monile (DM), Polygonati Officinalis (PO), Polygonati Rhizoma (PR) have been used to treated a variety condition/diseases in traditional oriental medicine. The present study was conducted to investigate the immunmodulatory effects of the water-extracted AR, LT, DH, PO and PR. In spleen cell proliferation assay, DH was significantly enhanced mitogenic activity compared with control group. In RT-PCR, DH ad PO induced IL-2 and IFNr cytokine gene expression in mouse spleen cells. Methotrexate(MTX), immune supression agent, was significantly inhibited mouse spleen cell proliferation(1600 mg/ml). In spite of MTX treatement, DH and PO sustained the spleen cell proliferation, In the flow cytometry analysis, DH stimulated mouse spleen cells showed an increase in B-cell phenotype (CD45R/B220). The water-extracted DH and PO inhibited NO production and iNOS expression in LPS-stimulated RAW 264.7 macrophage cell. DH induced IL-2 and IFNg gene expression in human peripheral mononuclear cells. The GC-MS analysis show that the main component of water-extracted DH was b-Nitroethyl alcohol. The main components of water-extracted PO were Dipirartril-tropico, Methyl sulfoxide and Demsodrox. These data suggest that among these extracts, DH has a protective effcet of immune suppression caused by MTX. DH may be enhance cellular and humoral immune response by the regulation of cytokine gene expression, NO production and B cell production.

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.351-355
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• 2008

Prodigiosin was isolated from marine bacteria Hahella chejuensis which has been recently discovered from Marado, Cheju Island, Republic of Korea. Immunosuppressive properties have been reported for prodigiosin members such as undecylprodigiosin, metacycloprodigiosin, prodigiosin, and its synthetic analogue PNU156804 (PNU). However, the effect of this agent on the function of macrophage and splenocyte has not been characterized in detail. In the present study, we examined the effects of prodigiosin for its ability to alter the function of murine macrophage and NK cell, and the proliferation of splenocytes. When thioglycollate-elicited macrophages pre-exposed to prodigiosin (1-50 ng/ml) were stimulated with LPS/IFN-$\gamma$, pretreatment with prodigiosin resulted in the inhibition of tumoricidal activity of macrophage in a concentration-dependent manner. Tumoricidal activity of NK cell was also inhibited by prodigiosin. Moreover, we found that prodigiosin was able to cause a dose-dependent inhibition of murine lymphocyte responsiveness to Con A and LPS although T-mitogenic response was the more sensitive one. Taken together, the present results point out that prodigiosin has a suppressive effect on the mitogen-induced proliferation of murine lymphocytes and the function of macrophage and NK cell.