• Molecules and Cells
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• v.45 no.6
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• pp.425-434
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• 2022

The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

• Food Science and Biotechnology
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• v.14 no.1
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• pp.147-151
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• 2005

Purified compound with intestinal immune system-modulating properties, GWE-2c, was isolated from methanol extract of Gelidium amansii by sequential procedures with silica gel column, LH-20 Sephadex gel column, and thin-layer chromatographies. In the presence of GWE-2c, strong immunoactivity in Peyers patch cell-mediated bone marrow cells was observed in vitro. In vivo intestinal immune-modulating activity was also enhanced by crude phenolic compound (GWE) of G. amansii in a dose-dependent manner. Investigation of production of several cytokines in Peyer's patch cells upon stimulation with GWE in vivo revealed the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-6 increased. Results suggest that the phenolic compound from G. amansii represents immunopotentiator and biological response modifier at in vitro and in vivo levels.

• Journal of Applied Biological Chemistry
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• v.55 no.1
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• pp.41-46
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• 2012

Arabinoxylan (Ara) rice bran has been shown to be a potent biological response modifier as manifested by stimulation of different arms of the immune system. We examined the effects of Ara rice bran and exercise on the immune function and cytokines in lipopolysaccharide (LPS)-stimulated rats. As the results, tumor necrosis factor-${\alpha}$ as representative inflammatory cytokines showed a significantly lower in Ara supplement group, thus the Ara rice bran had a higher inhibitory activity than the both exercise and control group. However, 4 weeks of exercise training significantly increased inflammatory reactions rather than treatment with Ara in LPS-treated rats. The Ara rice bran acted to decrease the inflammatory reaction. These results suggest that the supplement of Ara rice bran is likely contribute to inflammation response and the Ara rice bran can be used as a possible safe alternative to the immunotherapeutic modalities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1277-1283
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• 2002

Silsosangami(SSG) is a formula of treaditional korean medicines as an effective biological response modifier for augmenting host homeostasis of body circulation. Little is known of the biological activity of SSG and previous studies have focused mainly on their anti-thrombosis8). There is a growing interest in the pharmacological potential of the SSG due to the recent finding by our group that SSG and each constituent herbs of SSG were able to inhibit NO and prostaglandin E2 (PGE2) synthesis in murine peritoneal macrophages stimulated with bacterial endotoxin. In this paper, the effects of SSG on platelet aggregation and hemolysis in human blood were studied. SSG provoked remarkable inhibiting effect on platelet aggregation, and APTT were sensitive to the presence of this SSG. Using an in vitro system, APTT was delayed with the increment of the concentrations of these seven compounds. These results suggested that SSG might be used as a novel antithrombotic therapeutic agents in post-myocardial infarction. A SSG reduced NO production in mouse peritoneal macrophages stimulated with lipopolysaccharide, without the influence on the activity of iNOS being observed. SSG significantly reduced mouse paw edema induced by carrageenan. Western blot analysis showed that SSG reduced the expression of iNOS. The results indicate that SSG exerts anti-inflammatory effects related to the inhibition of NO production, which could be due to a decreased expression of iNOS.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3469-3472
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• 2013

Extract of Lentinula edodes mycelia (LEM) is currently utilized as an oral biological response modifier (BRM) medicine for cancer patients. However, its effectiveness for breast cancer patients with postoperative adjuvant hormone therapy has not yet been scientifically verified. In this study, we investigated the influence of LEM on the quality of life (QOL) and immune response in breast cancer patients undergoing postoperative adjuvant hormone therapy. Twenty patients were studied in total. They received only hormone therapy in the first 4 weeks followed by hormone therapy and LEM during the next 8 weeks. Laboratory tests, QOL score and peripheral blood cytokine production levels were evaluated during the study period. No changes in QOL or cytokines were noted after the first 4 weeks. In contrast, during the following combined therapy period, improvements were noted in QOL and cytokine levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant use of LEM with postoperative adjuvant hormone therapy improves the QOL and immune function of patients.

• Food Science and Biotechnology
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• v.14 no.4
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• pp.479-486
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• 2005

Arabinoxylan, a complex polysaccharide in cereal cell walls, has recently received research attention as a biological response modifier. The immunomodulating effect of arabinoxylans from rice bran (AXrb) was studied using a combined process of extrusion and commercial hemicellulase treatment in order to elucidate the augmentation mechanism of cell-mediated immunity in vitro. The cytotoxicity of mouse spleen lymphocytes against YAC-1 tumor cells was significantly enhanced by treatment with AXrb at $10-100\;{\mu}g/mL$. In an attempt to investigate the mechanism by which AXrb enhance NK cytotoxicity, we examined the effect of AXrb on cytokine production by spleen lymphocytes. Culture supernatants of the cells incubated with AXrb were collected and analyzed for IL-2 and IFN-${\gamma}$ synthesis by ELISA. IL-2 and IFN-${\gamma}$ production were increased significantly. These results suggest that AXrb may induce Th1 immune responses. Macrophages play an important role in host defenses against tumors by killing them and producing secretory products, which protect against bacterial, viral infection and malignant cell growth. AXrb were examined for their ability to induce secretory and cellular responses in murine peritoneal macrophages. When macrophages were treated with various concentrations ($10-100\;{\mu}g/mL$) of AXrb, AXrb induced tumoricidal activity, as well as increasing phagocytosis and the production of NO, $H_2O_2$, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These results indicate that reactive oxygen species, reactive nitrogen species, and inflammatory cytokines are likely to be the major mediators of tumoricidal activity in AXrb-treated macrophages. Therefore, AXrb may be useful in cancer immunotherapy and it is anticipated that AXrb obtained using extrusion and subsequent enzyme treatment can be used as an ingredient in nutraceuticals and cereal-based functional food.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.7
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• pp.1092-1097
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• 2004

The objective of the current study was to determine the effects of the crude polysaccharide isolated from fruit body of Pleurotus eryngii on mouse splenocytes, B cells, and macrophages in vitro. The crude polysaccharides directly induced the proliferation of spleen cells in a dose-dependent manner and increased IL-6 and IFN-${\gamma}$ synthesis. The crude polysaccharides also increased the proliferation of B cells in a dose-dependent manner. The production of immunoglobulin Gl, G2a and IgG3 in the presence of the crude polysaccharides was increased progressively in the culture supernatant. When the crude polysaccharide were used in macrophage cell line (RA W264.7) stimulation, there were marked induction of NO synthesis in a dose-dependent manner and IL-6, TNF- r and GM-CSF synthesis. These results suggest that the crude polysaccharide isolated from fruit body of Pleurotus eryngii seem to act as a potent immunomodulator causing augmentation of immune cell activity, and thus could be used as a biological response modifier having possible therapeutic effects against immunological disorders, without any side effects.

• Microbiology and Biotechnology Letters
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• v.24 no.1
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• pp.37-43
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• 1996

Augmentation of antitumor activity of antitumor drugs in combination with Lactobacillus casei HY2782 (LC2782) was studied against Sarcoma-180 (S-180) and Lewis lung carcinoma (3LL). Antitumor drugs used in this study were 5-fluorouracil (5-fu) and cyclophosphamide (CP). The prolongation effect of LC2872 on the life span of mouse intraperitoneally implanted with S-180 was stronger than that of OK-432 and BCG, while the inhibitory effect of OK-432 and BCG on the growth of 3LL solid tumor was a little stronger than that of LC2782. Average survival rates of mice administrated LC2782, OK-432 and BCG were 192%, 141%, and 112%, respectively, when that of the control was 100%, Intralesional administration of 5-Fu, CP, 5-Fu+LC2782 and CP+LC2782 resulted in 93%, 69%, 99% and 73% inhibition rates against 3LL solid tumor proliferation. The combination therapy of 5-Fu or CP with LC2782 significantly prolonged the life span of S-180-inoculated ICR mice. Average survival rates of mice administrated 5-Fu and CP alone were 115% and 99%. Furthermore, survival rates of mice administrated 5-Fu and CP in combination with LC2782 were 226% and 244%, respectively.

• Microbiology and Biotechnology Letters
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• v.31 no.2
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• pp.165-170
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• 2003

Hot water extracts of Chlorella capsulata(CCE) is a biological response modifier (BRM) which exhibits neuronal differentiation activity. The effect of CCE on the growth of nerve cells, PC12 was observed as follows: The viable cell density in adding CCE was increased up to 2.5 times, compare to that in no addition. The neurite of the cells was also lengthened up to 40 $\mu\textrm{m}$ longer than 5 $\mu\textrm{m}$ in no addition. The number of neurite-bearing cells were about four times higher than that in no addition.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3195-3201
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• 2015

Objectives: To investigate the effects of betaine on HeLa cell growth and apoptosis and molecular mechanisms. Materials and Methods: Concentrations of 0.1, 1.0, 5.0, 20.0, 100.0 mg/ml of betaine were used to evaluate the anticancer efficacy for HeLa cells respectively, and MCF-10A was also detected as a normal diploid cell control. Results: We found that proliferation of HeLa cells was inhibited significantly upon exposure to increasing betaine levels with the MTT test (p<0.05). The percentage of S phase cells in the low dose groups (<5mg/ml) were distinctly higher than in high dose groups, and the rates of Sub-G1 phase were the opposite (p<0.01); A high concentration of betaine (>5.0mg/ml) significantly promoted the apoptosis of HeLa cells (p<0.01). SOD activities of the low dose groups were slightly higher than the control group (p<0.05) and there were obvious synchronicity and correlation among the expression of promoting apoptosis genes Bax, P53, Caspase 3 and apoptosis suppression gene Bcl-2. In response to an apoptosis-inducing stimulus, p53 and cyclin D1 could be activated with blockage of the cell cycle at G1/S or S/G2 checkpoints. Conclusions: Our data showed that betaine could promote HeLa cells proliferation in vitro at low concentrations. In contrast, high concentrations could significantly inhibit cell growth and migration, and induce apoptosis of HeLa cells through caspase 3 signaling and further promoted necrosis. This might imply that betaine exhibits tumoricidal effects and acts as a biological response modifier in cancer treatment by inducing apoptosis and cell cycle arrest in a dose and time-dependent manner.