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Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

  • TaeKyung Nam;Wonku Kang;Sangtaek Oh
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1206-1212
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    • 2023
  • The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

Study on the Structure of the Korea-Japan Joint Development Zone by Means of Geophysical Data (지구물리 자료를 이용한 한일공동개발구역 일원의 구조 해석)

  • Jeongwon Ha;Sik Huh;Hyoungrea Rim
    • Geophysics and Geophysical Exploration
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    • v.27 no.1
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    • pp.23-36
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    • 2024
  • In this study, we analyze the structure of the Korea-Japan Joint Development Zone (JDZ) using gravity, magnetic, and seismic data. Gravity and magnetic data analysis confirmed that the Jeju Basin exhibits low anomalies compared to adjacent areas. We applied the total gradient to the Bouguer anomaly to identify basin boundaries, and computed the analytic signal from the total magnetic anomaly data to enhance the edges of the magnetic anomalies. The Taiwan-Sinzi Belt, exhibits high magnetic anomalies and crosses the center of the JDZ in the northeast-southwest direction; we presume that intrusive rocks are sporadic in the JDZ. The 3D inversion results of the gravity and magnetic data show a strong correlation between magnetic susceptibility and density (i.e. a low-density zone in the Jeju Basin and the Ho Basin, and a high magnetic susceptibility distribution in the Taiwan-Sinzi Belt). Comparison of the density and seismic profiles of the Jeju Basin shows that high densities are associated with sill, horst, and basement highs, whereas low densities are associated with basement low and grabens. These results suggest that interpretations based on seismic, gravity and magnetic data can effectively reveal the subsurface structure of the JDZ.

Analysis of Fish Community Structures and Guild Compositions in Walpyung Conservation Park (월평공원 생태 보존지역의 어류군집 구조 및 어류길드 특성 분석)

  • Jo, Hyun-Kyu;Choi, Ji-Woong;An, Kwang-Guk
    • Korean Journal of Ecology and Environment
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    • v.45 no.3
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    • pp.263-270
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    • 2012
  • The objectives of the study were to determine fish fauna and compositions during 2010~2011 in Walpyung Conservation Park along with analysis of fish community structures and trophic and tolerance guilds. Total number of species and individuals sampled were 31 and 2667, respectively and dominant species was Zacco platypus (46.6%) and subdominant species was Acheilognathus lanceolatus (8.7%), which were composed of >50% of the total. Total number of Korean endemic species including Microphysogobio yaluensis was 10 and the proportion of the individuals was 8.7%. Also, natural monument No. 454 of Iksookimia choii, which is endangered species and legal protected species, was sampled and the total number of individuals was only three. According to the analysis of fish community structures, species richness index in the mid-stream reach ($M_r$) was 3.145, which is higher than any other stream reaches ($U_r$ and $D_r$). In contrast, the richness index was 2.180 in the up-stream reach ($U_r$), which is minimum among the sampling sites. Species diversity index was 1.785 and 1.975, respectively in the headwater ($U_r$) and mid-stream reach ($M_r$) and the low values in the down-stream reach ($D_r$, 1.660) were due to the influences of pointsource (i.e., road construction) and non-point sources (sporadic agricultural spots). According to analysis of tolerance guilds, the proportion of tolerant species (TS), based on the number of individuals, was composed of 64.2% and sensitive species (SS) was only 3.3%, indicating a predominance of tolerant fishes in the compositions. The proportion of omnivore species (OS), however, was composed of 64.0% and insectivore species (IS) was 29.3%, indicating a predominance of omnivore fishes in the stream. The high proportions of tolerant and omnivore species in this stream indicates that the water quality and physical habitat environments were degradated in this system. For these reasons, especially natural monument and endemic fish species in this region should be protected from the massive constructions and required to provide efficient stream management strategies.