• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.119.2-119.2
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• 2001

• Journal of Microbiology and Biotechnology
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• 제32권10호
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• pp.1355-1355
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• 2022

• 한국식품영양과학회지
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• 제32권3호
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• pp.428-436
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• 2003

Carotenoids는 항암 효과가 있는 것으로 알려져 있으나 각각의 carotenoids가 대장암에 미치는 영향에 대해서는 명확하게 밝혀진 바가 없다. 본 연구에서는 4가지 종류의 carotenoids가 인간의 대장에서 유래한 암세포인 HT-29 세포의 증식에 미치는 영향을 조사하였다. $\alpha$-carotene, $\beta$-carotene, lutein lycopene을 농도를 달리 하여 세포 배양액 에 첨가하여 살아있는 세포의 수를 측정한 결과 $\beta$-carotene는 세포의 증식을 다소 증가시키는 반면 $\alpha$-carotene, lutein, lcopene은 세포의 증식을 감소하였다. 세포의 증식을 억제한 carotenoids 중에서 lycopene이 그 효과가 가장 컸다. ErbB receptor family는 세포의 증식을 촉진하고 대장암에서 그 발현이 증가된 것으로 보고되었기 때문에 lycopene이 heregulin-ErbB3 signaling을 억제하는지를 조사하였다. Lycopene는 ErbB2 단백질을 감소하였고 ErbB3 단백질의 변화를 초래하였다. Heregulin을 첨가하여 인산화를 유도한 경우 ErbB3의 인산화, ErbB3와 p85의 결합, Akt 인산화가 lycopene에 의해 억제되었다. 이 결과들은 carotenoids 중 lycopene이 대장암 세포 증식 억제 효과가 가장 크고, 대장암 세포의 DNA 합성을 억제하고 apoptosis를 유도하는 lycopene효과의 일부는 Erb-B3와 Akt의 인산화 감소에 기인하는 것임을 나타낸다.

• 생명과학회지
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• 제29권11호
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• pp.1251-1257
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• 2019

본 연구에서는 펩티도글리칸이 단핵세포의 $TNF-{\alpha}$ 발현에 미치는 영향을 조사하였고, 또한 펩티도글리칸에 의한 $TNF-{\alpha}$ 발현에 관련된 세포의 요소들을 연구하였다. 사람의 단핵세포주인 THP-1 세포를 펩티도글리칸에 노출시키는 경우 $TNF-{\alpha}$ 분비 증가뿐만 아니라 $TNF-{\alpha}$ 유전자 전사를 유도하는 결과를 가져왔다. TLR-2/4의 억제제인 OxPAPC은 펩티도글리칸에 의한 $TNF-{\alpha}$의 발현을 저해하였다. 그리고 U0126, SB202190, SP6001250, LY294002, Akti IV, rapamycin, NAC, DPI 같은 약리학적 저해제 또한 $TNF-{\alpha}$ 발현을 유전자/단백질 수준에서 상당히 약화시켰다. 그러나 polymyxin B는 $TNF-{\alpha}$ 발현에 영향을 주지않았다. 따라서 펩티도글리칸이 TLR-2, PI3K, Akt, mTOR, MAPKs, ROS 등을 통하여 단핵세포의 $TNF-{\alpha}$ 발현을 증가시킴을 확인하였다.

• 대한화장품학회지
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• 제48권1호
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• pp.11-24
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• 2022

Piper methysticum 뿌리의 에탄올 추출물은 멜라닌 세포 자극 호르몬 활성화 B16 흑색종 세포에서 멜라닌 생성을 억제하는 것으로 알려져 왔다. 이 추출물로부터 분리한 flavokawain B (FKB)와 flavokawain C (FKC)는 항멜라닌 생성 활성을 기반으로 멜라닌 생성을 억제하는 것으로 밝혀져 있다. 본 연구는 melan-a 세포에서의 멜라닌 합성에 대한 FKB 및 FKC의 억제 및 그 과정을 알아보고자 하였다. FKB와 FKC는 각각 10 μM, 5 μM 농도에서 melan-a 세포의 멜라닌 생성을 억제하였다. 그러나 FKB와 FKC 모두 세포 외 타이로시네이즈 활성은 억제하지 않았다. FKB는 타이로시네이즈 (tyrosinase, Tyr), 타이로시네이즈 연관 단백질 1 (tyrosinaserelated protein 1, TRP-1)과 2(tyrosinase-related protein 2, TRP-2), microphthalmia-associated transcription factor (MITF)의 단백질 발현량을 감소시켰으며 Tyr와 TRP-1의 mRNA 발현량을 감소시켰다. FKC는 TRP-2와 MITF의 단백질 발현량을 감소시켰으며 Tyr와 TRP-1의 mRNA 발현량을 감소시켰다. Tyr와 TRP-1의 감소된 발현은 주요 멜라닌 생성 단백질을 조절하는 MITF발현 감소로 인한 것임을 예상할 수 있었다. 다만 MITF의 mRNA 발현량은 FKB와 FKC 처리에 의해 변하지 않았기 때문에, MITF의 분해를 조절한다고 알려진 세포 외 신호 조절 키나아제(ERK)/AKT 인산화에 대한 FKB와 FKC의 영향을 확인하였다. FKB와 FKC는 AKT의 인산화를 증가시키지는 않았지만 ERK1/2의 인산화를 유의미하게 증가시켰다. 이러한 결과는 FKB와 FKC가 다양한 색소 침착 증상들에 대한 잠재적인 미백제로 도움이 될 수 있음을 말해준다.

• Tuberculosis and Respiratory Diseases
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• 제53권6호
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4635-4639
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• 2013

Multi-drug resistance (MDR) is an essential aspect of human lung cancer chemotherapy failure. Recent studies have shown that vinorelbine is involved in underlying processes in human tumors, reversing the MDR inseveral types of cancer cells. However, the roles and potential mechanism are not fully clear. In this study, we explored effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549/DDP cells. We found that vinorelbine increased drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase ${\pi}$ (GST-${\pi}$) in A549/DDP cells. At the same time, we also established downregulation of p-Akt and decreased transcriptional activation of NF-${\kappa}B$ and twist after vinorelbine treatment. The results indicated that vinorelbine might be used as a potential therapeutic strategy in human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3781-3789
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• 2012

Background: Pancreatic cancer is one of the most aggressive tumors with a dismal prognosis. The membrane cytoskeletal crosslinker Ezrin participates in several functions including cell proliferation, adhesion, motility and survival. There is increasing evidence that Ezrin is overexpressed in vast majority of malignant tumors and regulates tumor progression. However, its roles in pancreatic cancer remain elusive. Methods: Three pairs of specific Ezrin siRNAs were designed and synthetized and screened to determine the most efficient one for construction of a hairpin RNA plasmid targeting Ezrin. After transfection into the Panc-1 pancreatic cancer cell line, real-time quantitative PCR and Western blotting were performed to examine the expression of mRNA and protein. The MTT method was applied to examine the proliferation and the drug sensibility to Gemcitabine. Flow cytometry was used to assess the cycle and apoptosis, while capacity for invasion was determined with transwell chambers. Furthermore, we detected phosphorylated-Erk1/2 protein and phosphorylated-Akt protein by Western blotting. Results: Real-time quantitative PCR and Western blotting revealed that Ezrin expression was notably down-regulated at both mRNA and protein levels by RNA interference (P< 0.01). Proliferation was inhibited and drug resistance to gemcitabine was improved (P< 0.05). Flow cytometry showed that the proportion of cells in the G1/G0 phase increased (P< 0.01), and in G2/M and S phases decreased (P< 0.05), with no apparent differences in apoptosis (P> 0.05). The capacity for invasion was markedly reduced (P< 0.01). In addition, down-regulating Ezrin expression had no effect on phosphorylated-Akt protein (P>0.05), but could decrease the level of phosphorylated-Erk1/2 protein (P< 0.05). Conclusions: RNA interference of Ezrin could inhibit its expression in the pancreatic cancer cells line Panc-1, leading to a potent suppression of malignant behavior in vitro. Assessment of potential as a target for pancreatic cancer treatment is clearly warranted.

• 치위생과학회지
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• 제19권4호
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• pp.254-260
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• 2019

Background: The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression. Methods: Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting. Results: Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2. Conclusion: Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.

• Journal of Ginseng Research
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• 제39권3호
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• pp.279-285
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• 2015

Background: Korean Red Ginseng has been used as a traditional oriental medicine to treat illness and to promote health for several thousand years in Eastern Asia. It is widely accepted that ginseng saponins, ginsenosides, are the major active ingredients responsible for Korean Red Ginseng's therapeutic activity against many kinds of illness. Although the crude saponin fraction (CSF) displayed antiplatelet activity, the molecular mechanism of its action remains to be elucidated. Methods: The platelet aggregation was induced by collagen, the ligand of integrin ${\alpha}_{II}{\beta}_I$ and glycoprotein VI. The crude saponin's effects on granule secretion [e.g., calcium ion mobilization and adenosine triphosphate (ATP) release] were determined. The activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38 MAPK, and phosphoinositide 3-kinase (PI3K)/Akt was analyzed by immunoblotting. In addition, the activation of integrin ${\alpha}_{II}b{\beta}_{III}$ was examined by fluorocytometry. Results: CSF strongly inhibited collagen-induced platelet aggregation and ATP release in a concentration-dependent manner. It also markedly suppressed $[Ca^{2+}]_i$ mobilization in collagen-stimulated platelets. Immunoblotting assay revealed that CSF significantly suppressed ERK1/2, p38, JNK, PI3K, Akt, and mitogen-activated protein kinase kinase 1/2 phosphorylation. In addition, our fraction strongly inhibited the fibrinogen binding to integrin ${\alpha}_{IIb}{\beta}_3$. Conclusion: Our present data suggest that CSF may have a strong antiplatelet property and it can be considered as a candidate with therapeutic potential for the treatment of cardiovascular disorders involving abnormal platelet function.