• 동의생리병리학회지
• /
• 제18권4호
• /
• pp.1147-1152
• /
• 2004

To investigate the anti-cancer effects of aqueous extract of Cheonkumwikyung-tang (CKWKT) on the growth of human lung carcinoma cell line A549, we performed various biochemical experiments such as the effects of CKWKT on the cell proliferation and viability, the morphological changes, the effects on expression of apoptosis and cell growth-regulatory gene products. Results obtained are as follow; CKWKT treatment declined the cell viability and proliferation of A549 cells in a concentration-dependent manner. The anti-proliferative effect by CKWKT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. CKWKT treatment induced apoptotic cell death of A549 cells in a concentration-dependent manner, which was associated with inhibition and/or degradation of apoptotic target proteins such poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ1. Western blot analysis revealed that the levels cyclin-dependent kinase inhibitor p21 expression were induced by CKWKT treatment in A549 cells. Taken together, these findings suggest that CKWKT-induced inhibition of human lung cancer cell proliferation is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products and CKWKT may have therapeutic potential in human lung cancer.

• Journal of Microbiology and Biotechnology
• /
• 제33권1호
• /
• pp.114-122
• /
• 2023

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling pathways have been attractive targets for disease treatment. However, the complicatedness and large involveness of the pathway often hampers pinpointing the specific targets of the metabolic process. In our current study, we investigated the differential metabolic regulation by the overexpression of the Wnt signaling pathway in a timely-resolved manner by applying high-throughput and un-targeted metabolite profiling. We have detected and annotated 321 metabolite peaks from a total of 36 human embryonic kidney (HEK) 293 cells using GC-TOF MS and LC-Orbitrap MS. The un-targeted metabolomic analysis identified the radical reprogramming of a range of central carbon/nitrogen metabolism pathways, including glycolysis, TCA cycle, and glutaminolysis, and fatty acid pathways. The investigation, combined with targeted mRNA profiles, elucidated an explicit understanding of activated fatty acid metabolism (β-oxidation and biosynthesis). The findings proposed detailed mechanistic biochemical dynamics in response to Wnt-driven metabolic changes, which may help design precise therapeutic targets for Wnt-related diseases.

• 한국자원식물학회지
• /
• 제33권4호
• /
• pp.263-270
• /
• 2020

이상의 연구 결과로 미루어 볼 때, 댕댕이나무 잎과 가지 추추출물은 대장암 세포주 HCT116과 SW480세포의 생육을 억제하였으나 열매추출물은 억제활성이 나타나지 않았다. 잎과 가지 추출물은 cell migration과 wound healing assay를 통해 비정상적인 세포증식 억제를 확인하였으며, β-catenin과 TCF4의 단백질 수준을 감소시켜 비정상적인 Wnt 신호전달을 억제를 통해 대장암세포의 생육을 억제하는 것으로 판단된다. 따라서 댕댕이나무 잎과 가지는 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다.

• Molecules and Cells
• /
• 제46권7호
• /
• pp.441-450
• /
• 2023

β-Catenin (Ctnnb1) has been shown to play critical roles in the development and maintenance of epithelial cells, including the retinal pigment epithelium (RPE). Ctnnb1 is not only a component of intercellular junctions in the epithelium, it also functions as a transcriptional regulator in the Wnt signaling pathway. To identify which of its functional modalities is critically involved in mouse RPE development and maintenance, we varied Ctnnb1 gene content and activity in mouse RPE lineage cells and tested their impacts on mouse eye development. We found that a Ctnnb1 double mutant (Ctnnb1^dm), which exhibits impaired transcriptional activity, could not replace Ctnnb1 in the RPE, whereas Ctnnb1^Y654E, which has reduced affinity for the junctions, could do so. Expression of the constitutively active Ctnnb1^∆ex3 mutant also suppressed the development of RPE, instead facilitating a ciliary cell fate. However, the post-mitotic or mature RPE was insensitive to the loss, inactivation, or constitutive activation of Ctnnb1. Collectively, our results suggest that Ctnnb1 should be maintained within an optimal range to specify RPE through transcriptional regulation of Wnt target genes in the optic neuroepithelium.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권1호
• /
• pp.215-220
• /
• 2014

Objective: To determine the expression of E-cadherin, ${\beta}$-catenin, and transcription factor 4 (TCF4) proteins in gastric diseases with relation to Helicobacter pylori infection. Methods: A total of 309 patients including 60 with superficial gastritis (SG), 57 with atrophic gastritis (AG) and 192 with gastric cancer (GC), were enrolled. The expression of E-cadherin, ${\beta}$-catenin, TCF4 proteins in the gastric mucosa was detected by immunohistochemistry and H. pylori infection by immunohistochemistry and PCR. Results: The expression rates of E-cadherin were significantly higher in SG and AG than in GC (P<0.01), while those of ${\beta}$-catenin in the nucleus were significantly lower in SG and AG than in GC (P<0.05). In GC cases, the expression rates of E-cadherin, ${\beta}$-catenin and TCF4 were significantly higher in the intestinal type than in the diffuse type (P<0.05). In GC patients, the expression rate of E-cadherin was significantly higher in the presence of H. pylori than in the absence of infection (P=0.011). Moreover, the expression level of TCF4 and ${\beta}$-catenin protein was significantly higher in the nucleus and cytoplasm in H. pylori positive than in H. pylori negative GC patients, especially in those with the intestinal type (all P < 0.05). Conclusion: The expression of E-cadherin and ${\beta}$-catenin progressively decreases during the process of GC tumorigenesis, while overexpression of TCF4 occurs. H. pylori infection is associated with a significant increase in the expression of E-cadherin and ${\beta}$-catenin in the cytoplasm and nucleus in GC patients, especially those with the intestinal type.

• 생명과학회지
• /
• 제32권5호
• /
• pp.331-339
• /
• 2022

멜라닌은 자외선과 같은 외부자극이 가해지면 피부 기저층에 존재하는 멜라닌 세포에서 피부를 보호하기 위한 방어기전으로써 생성이 된다. 하지만 과도한 자외선 노출로 멜라닌이 필요이상으로 생성이 되면 기미, 주근깨, 검버섯과 같은 색소침착 및 색소성 피부장애를 유발할 수 있다. 최근에는 부작용이 적은 식물 추출물을 대상으로 미백소재를 찾기 위한 연구들이 활기를 띠고 있다. 이에 본 연구에서는 국내 서식 염생식물인 갯사상자 추출물을 이용하여 B16F10 흑색종 세포에서 피부 색소 멜라닌 생성 억제에 미치는 효과를 확인하였다. 갯사상자 추출물 처리시 tyrosine 및 L-DOPA 산화를 농도 의존적으로 저해하였으며 세포 내의 멜라닌 생성을 담당하는 tyrosinase, tyrosinase-related protein-1, -2 발현을 억제하였다. 이는 갯사상자 추출물이 α-MSH에 의한 세포신호 전달 경로인 GSKβ/β-catenin 및 PKA/CREB 조절에 의한 것으로 밝혀졌다. 따라서 갯사상자 추출물은 GSKβ/β-catenin 및 PKA/CREB 기전을 통해 멜라닌 합성을 억제하여 미백 효능 지닌 천연물 유래 기능성 화장품 소재로서 활용 가능할 것으로 사료된다.

• Experimental and Molecular Medicine
• /
• 제50권12호
• /
• pp.3.1-3.14
• /
• 2018

Type 1 diabetes mellitus (T1DM) is a pathological condition associated with osteopenia. $WNT/{\beta}$-catenin signaling is implicated in this process. Trabecular and cortical bone respond differently to $WNT/{\beta}$-catenin signaling in healthy mice. We investigated whether this signaling has different effects on trabecular and cortical bone in T1DM. We first established a streptozotocin-induced T1DM mouse model and then constitutively activated ${\beta}$-catenin in osteoblasts in the setting of T1DM (T1-CA). The extent of bone loss was greater in trabecular bone than that in cortical bone in T1DM mice, and this difference was consistent with the reduction in the expression of ${\beta}$-catenin signaling in the two bone compartments. Further experiments demonstrated that in T1DM mice, trabecular bone showed lower levels of insulin-like growth factor-1 receptor (IGF-1R) than the levels in cortical bone, leading to lower $WNT/{\beta}$-catenin signaling activity through the inhibition of the IGF-1R/Akt/glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) pathway. After ${\beta}$-catenin was activated in T1-CA mice, the bone mass and bone strength increased to substantially greater extents in trabecular bone than those in cortical bone. In addition, the cortical bone of the T1-CA mice displayed an unexpected increase in bone porosity, with increased bone resorption. The downregulated expression of WNT16 might be responsible for these cortical bone changes. In conclusion, we found that although the activation of $WNT/{\beta}$-catenin signaling increased the trabecular bone mass and bone strength in T1DM mice, it also increased the cortical bone porosity, impairing the bone strength. These findings should be considered in the future treatment of T1DM-related osteopenia.

• 한국응용과학기술학회지
• /
• 제37권4호
• /
• pp.674-681
• /
• 2020

The root of Codonopsis lanceolata has been used in traditional medicine. This study was conducted to confirm the comparative effect of ethanol solvent extraction (CLE) and supercritical carbon dioxide extraction (CLS) of C. lanceolata roots. CLS had higher antioxidant than CLE. For supercritical co-solvent modified carbon dioxide extraction (CLS), it were extracted at 250 bar 50℃ 150 min at a flow rate of ethyl alcohol 3 mL/min for 90min. In addition, CLS inhibited the adipocyte differentiation of 3T3-L1 cells. When treated with the extract at a concentration of 100 ㎍/mL, the Wnt/β-catenin pathway reporter luciferase activity of HEK 293-TOP cells increased approximately by 3-folds compared to that of the untreated control group. Also, the treatment by CLS (50 ㎍/mL) showed a significant increase of involucrin expression. These results indicate that supercritical carbon dioxide extract of C. lanceolatamay serve as a cosmeceutical agent for improving skin barrier function and the treatment of obesity.

• 대한두개안면성형외과학회지
• /
• 제21권3호
• /
• pp.176-179
• /
• 2020

Pilomatricoma is a benign tumor arising from the primitive basal cells of the epidermis that differentiate into hair matrix cells. Mutations in the CTNNB1 gene, which encodes β-catenin (a protein involved in hair growth), play an etiological role in the development of pilomatricoma. A 34-year-old woman presenting with a mass in the right parotid region underwent an excisional biopsy. The mass was conclusively diagnosed as pilomatricoma. During pregnancy, the mass grew from 1 cm to 5 cm in diameter and was accompanied by pain and tenderness. The growth may have been facilitated by the increased production of estrogen and progesterone, which bind to receptors located in the outer root sheath cells of the hair follicles. No recurrence was observed during 6 months of follow-up.

• BMB Reports
• /
• 제56권2호
• /
• pp.65-70
• /
• 2023

Prominin-1 (PROM1), also called CD133, is a penta-span transmembrane protein that is localized in membrane protrusions, such as microvilli and filopodia. It is known to be expressed in cancer stem cells and various progenitor cells of bone marrow, liver, kidney, and intestine. Accumulating evidence has revealed that PROM1 has multiple functions in various organs, such as eye, tooth, peripheral nerve, and liver, associating with various molecular protein partners. PROM1 regulates PKA-induced gluconeogenesis, TGFβ-induced fibrosis, and IL-6-induced regeneration in the liver, associating with Radixin, SMAD7, and GP130, respectively. In addition, PROM1 is necessary to maintain cancer stem cell properties by activating PI3K and β-Catenin. PROM1-deficienct mice also show distinct phenotypes in eyes, brain, peripheral nerves, and tooth. Here, we discuss recent findings of PROM1-mediated signal transduction.