• Korean Journal of Pharmacognosy
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• v.53 no.1
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• pp.21-28
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• 2022

Sparassis crispa is an edible mushroom that has been widely utilized in Japan and Korea. It has various biological activities, such as anti-hypertensive, anti-allergic, anti-diabetic, anti-inflammatory, anti-angiogenic, and anti-cancer effects. In this study, we investigated the anticancer activity and underlying molecular mechanism of chloroform fraction of methanol extract of S. crispa (CESP) against cervical cancer stem cells (CSCs), which contribute to tumor initiation, recurrence, and resistance to therapy of human cervical cancer. CESP effectively inhibited the proliferation, tumorsphere formation, and migration of HeLa-derived cervical CSCs by promoting apoptosis. In addition, CESP significantly downregulated the expression of key cancer stemness markers, including integrin α6, CD133, CD44, ALDH1A1, Nanog, Oct-4, and Sox-2, in HeLa-derived cervical CSCs. Furthermore, CESP remarkably suppressed in vivo tumor growth of HeLa-derived cervical CSCs in a chick embryo chorioallantoic membrane (CAM) model. Therefore, our findings suggest that CESP has potential as a natural medicine for the prevention and treatment of cervical cancer by targeting CSCs.

• Biomedical Science Letters
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• v.29 no.4
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• pp.336-343
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• 2023

Lung cancer is one of the cancers with high mortality and incidence rates worldwide. Although, various anticancer research efforts are underway to completely treat cancer, the challenge against it remains in the inability to eliminate cancer stem cells (CSCs), leading to difficulties in curing the cancer and resulting in recurrence. As a result, there is a growing interest in the discovery of new biomarkers and therapeutic molecules that can simultaneously target both cancer cells and CSCs. From this point of view, we focused on fibronectin leucine rich transmembrane protein 3 (FLRT3), one of the genes known to be present in human lung cells and the discovery from our previous cancer proteomic analysis study. This study aimed to evaluate the potential of FLRT3 as a specific therapeutic biomarker for lung cancer and Lung Cancer-derived-Stem Cells (LCSC). Also, to estimate the biological function of FLRT3 in cancer and LCSC, short hairpin RNA (shRNA) was generated and showed the ability of the decreased-cell migration and cell proliferation of lung cancer through ERK signaling pathway when FLRT3 was knock-downed. In conclusion, our study is the first to report that FLRT3 has the potential as therapeutic biomarker for the treatment of lung cancer and LCSC.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.29.1-29.20
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• 2020

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.

• Journal of Periodontal and Implant Science
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• v.26 no.4
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• pp.841-858
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• 1996

Epidermal growth factor(EGF) is one of polypeptide growth factors. EGF has been reported as a biological mediator which regulates activities of wound healing process including the cell proliferation, migration and metabolism. The purposes of this study is to evaluate the effects of EGF on the human periodontal ligament cells and human gingival fibroblast cells that promote regeneration of periodntal tissue. The mitogenic effects of epidermal growth factor on human periodontal ligament cells and human gingival fibroblasts were evaluated by determining the incorporation of 5-Bromo-2'-deoxy-uridine into DNA of the cells in a dose dependent manner. The prepared cells were the primary cultured gingival fibroblast and periodontal ligament cells from humans, the fourth or sixth subpassages were used in the experiments. Cells were seeded in DMEM containing 10% FBS. 1, 10, 50, 100, $200{\eta}g/ml$ and epidermal growth factor were added to the quiescent cells for 24 hours, 48 hours and 72 hours. They were labeled with $10\{mu}l/200{\mu}l$ 5-Bromo-2'-deoxy-uridine for the last 6 hours of each culture. The results of the five determinants were presented as mean and S.D.. The results were as follows : The DNA synthetic activity of human gingival fibroblasts were increased dose dependently by epidermal growth factor at 24 hours, 48 hours and 72 hours. The mitogenic effects were similar at the 24 and 48 hours of epidermal growth factor, but the DNA synthetic activity of human gingival fibroblasts generally decreased at 72 hours. The DNA synthetic activity of human periodontal ligament cells were increased dose dependently by epidermal growth factor at 24 hours but the DNA synthetic activity decreased at $200{\eta}g/ml$ of each hour. Generally the maximum mitogenic effects were observed at the 48 hours application of epidermal growth factor. The DNA synthetic activity of human periodontal ligament cells generally decreased lower at 24, 72 hours than at 48 hours the application of epidermal growth factor. In the comparison of DNA synthetic activity between human gingival fibroblasts and human periodontal ligament cells, human periodontal ligament cells had slightly higher proliferation activity than human gingival fibroblasts for a longer time at the high dosage of the epidermal growth factor. In conclusion, epidermal growth factor have important roles in the stimulation of DNA synthesis in human periodontal ligament cells and human gingival fibroblasts, and thus may be useful for clinical applications in periodontal regenerative procedures.

• 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.

• Journal of fish pathology
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• v.18 no.3
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• pp.277-285
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• 2005

Israeli carps were intraperitoneally injected with an aqueous extract of red ginseng (RG) at five different concentrations (0, 1, 10, 25 and 50 mg/kg of body weight). The fish were sacrificed after 3 days and measured the neutrophil activity and plasma components. The activity of lysozyme, Ht, TIC and NBT reduction were significantly enhanced in the concentrations of more than 10 mg/kg. Further attempts were made to measure the effects of RG on leucocyte function at five different concentrations (1-100 ${\mu}g/m{\ell}$), in vitro. The proliferation of lymphocytes co-incubated with phytohaemagglutin (PHA) and concanavalin A (Con A) was significantly increased at 10 ${\mu}g/m{\ell}$ concentration, but suppressed at the highest concentration (100 ${\mu}g/m{\ell}$). RG alone or with lipopolysaccharide (LPS) had no effect on proliferation at any concentrations tested. Migration and reactive oxygen intermediates (ROI) production of leucocytes were enhanced in all concentration higher than 10 ${\mu}g/m{\ell}$. These results suggest that the RG activates the leucocyte function and may be able to be used as a stimulant of fish innate defences.

• Archives of Plastic Surgery
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• v.37 no.4
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• pp.340-345
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• 2010

Purpose: Recently, bioceramics have become popular as a substitute graft material for reconstruction of bony defect after trauma or tumor surgery. Among the bioceramic materials, hydroxyapatite (HA) is favored due to its biocompatibility. HA scaffold is composed of the interconnected reticular framework, macropores and micropores. Macropores play an important role in cell migration, nutrients supply and vascular ingrowth. On the other hand, a number of micropores less than $10{\mu}m$ form an irregular surface on HA scaffolds, which prevents the osteoblast from adhering and proliferating on the surface of HA scaffold. Methods: In this study, three different groups were designed for comparison. In the first group (group A), conventional method was used, in which HA pellet was applied without surface pretreatment. The second group (group B) was given a HA pellet that has been coated with crystalline HA solution prior to application. In the third group (group C), the same method was used as the second group, where the pretreated HA pellet was heated ($1250^{\circ}C$, 1 hour) before application. Osteoblast-like cells ($2{\times}10^4$/mL) were scattered onto every pellet, then they were incubated in 5% $CO_2$ incubator at $37^{\circ}C$ for twelve days. During the first three days, osteoblast cells were counted using the hemocytometer daily. ALP activity was measured on the 3, 6, 9 and 12 culture days using the spectrophotometer. Results: Under SEM, group A showed a surface with numerous micropores, and group B revealed more rough crystal surface. Group C revealed a fused crystal appearance and flattened smooth surface. In proliferation and ALP activity of osteoblast cells, group C showed better results compared to group B. Group A which lacks pretreatment of the surface showed less osteoblast proliferation and ALP activity than group C, but showed better results than group B. Conclusion: We found that crystallized HA with heat treatment method enhances the osteoblasts proliferation and differentiation on the surface of HA pellets.

• Toxicological Research
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• v.27 no.4
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• pp.253-259
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• 2011

Transforming growth factor ${\beta}$ (TGF-${\beta}$) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-${\beta}$ is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-${\beta}$, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/$ER{\alpha}$ and TGF-${\beta}$ pathway. Especially, based on the E2-mediated inhibition of TGF-${\beta}$ signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-${\beta}$ signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF-${\beta}$ receptor2 (TGF-${\beta}$ R2) in TGF-${\beta}$ signaling pathway. However, the expression level of TGF-${\beta}1$ and TGF-${\beta}$ receptor1 (TGF-${\beta}$ R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-${\beta}$ signaling pathway. As a result of downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-${\beta}$ signaling via the downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-${\beta}$ signaling.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.49 no.2
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• pp.183-192
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• 2023

In this study, we investigated the antioxidant activity, anti-inflammatory activity, whitening, moisturizing, wound-healing, cell proliferation and cell protective effects of 70% EtOH and hot water extract from Scutellaria baicalensis. For the anti-oxidative test, the 70% EtOH and hot water extract showed DPPH radical scavenging activities. In the anti-inflammatory tests, 70% EtOH and hot water extract inhibited the production of NO, pro-inflammatory cytokine (IL-6) and prostaglandin (PGE₂). In addition, it was confirmed that the 70% EtOH and hot water extract inhibited the melanin production, and increased production of hyaluronic acid (HA), a moisturizing factor. As a result of cell migration and proliferation assay, 70% EtOH extract promoted the cell growth in HaCaT cell. Additionally, 70% EtOH and hot water extract showed cell protective effects against UVB, and 70% EtOH extract also showed cell protective effects agianst blue light. Based on these results, it is concluded that the 70% EtOH and hot water extract from Scutellaria baicalensis could be potentially applicable as anti-oxdiative, anti-inflammation, whitening, moisturizing, wound-healing, cell proliferation and cell protective effects in cosmetic natural materials.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.4
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• pp.750-756
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• 2008

Supernumerary teeth are frequently found in the anterior portion of the maxilla and develop as a result of abnormal proliferation of the dental lamina during tooth germ formation, caused by genetic or environmental factors. They may result in various complications, such as eruption interference, displacement, rotation of adjacent teeth, diastema, eruption into the nasal cavity, and development of dentigerous cyst. The optimal time for surgical extraction of supernumerary teeth has been a controversial issue. Someone prefer early surgical extraction because supernumerary teeth can cause eruption interference and displacement of adjacent teeth, eventually altering occlusion. Others prefer to delay surgical extraction until $8{\sim}10$ years of age in consideration of root maturation of the adjacent teeth and also patient's behavior. When surgical extraction of supernumerary teeth is postponed, there is possibility that impacted supernumerary teeth in the inverted or horizontal position move toward the nasal cavity, hard palate, or premolar area. When such intraosseous tooth migration is combined with the vertical growth of the maxilla, surgical approach becomes even harder. Therefore, possibility of intraosseous tooth migration should be considered as an important factor when deciding appropriate time for surgical extraction. We are presenting cases of mesiodens which showed intraosseous migration during $6{\sim}7$ years of follow-up period since the first diagnosis had been made at the $2{\sim}3$ years of age.