• Title/Summary/Keyword: HS-146

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HS-146, a novel phosphoinositide 3-kinase α inhibitor, induces the apoptosis and inhibits the metastatic ability of human breast cancer cells

  • Ok Hyeon Kim;Ju-Hee Lee;Shinmee Mah;Sung Yun Park;Sungwoo Hong;Soon-Sun Hong
    • International Journal of Oncology
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    • v.56 no.6
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    • pp.1509-1520
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    • 2020
  • The phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in human cancer as it regulates critical cellular functions, such as survival, proliferation and metabolism. In the present study, a novel PI3Kα inhibitor (HS-146) was synthesized and its anticancer effects on MCF-7, MDA-MB-231, SKBR3 and BT-474 human breast cancer cell lines were confirmed. HS-146 was found to be most effective in inhibiting the proliferation of MCF-7 cells and in inducing cell cycle arrest in the G0/G1 phase by downregulating cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)2 and Cdk4, and upregulating p21Waf1/Cip1 protein levels in this cell line. The induction of apoptosis by HS-146 was confirmed by DAPI staining and western blot analysis. Cell shrinkage and nuclear condensation, which are typical morphological markers of apoptosis, were increased by HS-146 in the MCF-7 cells in a concentration-dependent manner, and HS-146 also increased the protein expression levels of cleaved poly(ADP-ribose) polymerase (PARP) and decreased the protein expression levels of Mcl-1 and caspase-7. In addition, HS-146 effectively decreased the phosphorylation levels of downstream PI3K effectors, such as Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), p70S6K1 and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression were also suppressed by HS-146 under hypoxic conditions, and HS-146 inhibited the migration and invasion of MCF-7 cells in a concentration-dependent manner. On the whole, the findings of the present study suggest that HS-146, a novel PI3Kα inhibitor, may be an effective novel therapeutic candidate that suppresses breast cancer proliferation and metastasis by inhibiting the PI3K/Akt/mTOR pathway.

The Correlation Between Adult Hypercholesterolemia, Abdominal Obesity, Hyperuricemia, and High-Sensitivity C-Reactive Protein (성인의 고콜레스테롤혈증과 복부비만에 대한 고요산혈증과 고감도 C-반응단백의 관련성)

  • Jae-Jung Kim
    • Journal of the Health Care and Life Science
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    • v.11 no.2
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    • pp.417-424
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    • 2023
  • This study aimed to analyze the association between hyperuricemia and hs-CRP in adults with hypercholesterolemia and abdominal obesity, utilizing data from the 7th Korea National Health and Nutrition Examination Survey. The subjects were classified into fourgroups based on hypercholesterolemia and abdominal obesity, and binary logistic regression analysis was conducted. The association between hyperuricemia and hs-CRP wasevident in the abdominal obesity group, with an OR 2.22 (95% CI 2.070-2.395). In thegroup with both conditions, the OR was 2.31 (95% CI 2.032-2.626). Stratified by gender, both conditions showed a higher OR in males 2.29 (95% CI 1.911-2.748), while in females, the abdominal obesity group exhibited a higher OR of 2.44 (95% CI 2.146-2.775), indicating a gender-specific difference. In conclusion, hyperuricemia and hs-CRP in adults with hypercholesterolemia and abdominal obesity demonstrated a significant association, suggesting their role as predictive factors for inflammatory responses.

Remediation of heavy metal-contaminated soils using eco-friendly nano-scale chelators

  • Lim, Heejun;Park, Sungyoon;Yang, Jun Won;Cho, Wooyoun;Lim, Yejee;Park, Young Goo;Kwon, Dohyeong;Kim, Han S.
    • Membrane and Water Treatment
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    • v.9 no.3
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    • pp.137-146
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    • 2018
  • Soil washing is one of the most frequently used remediation technologies for heavy metal-contaminated soils. Inorganic and organic acids and chelating agents that can enhance the removal of heavy metals from contaminated soils have been employed as soil washing agents. However, the toxicity, low removal efficiency and high cost of these chemicals limit their use. Given that humic substance (HS) can effectively chelate heavy metals, the development of an eco-friendly, performance-efficient and cost-effective soil washing agent using a nano-scale chelator composed of HS was examined in this study. Copper (Cu) and lead (Pb) were selected as target heavy metals. In soil washing experiments, HS concentration, pH, soil:washing solution ratio and extraction time were evaluated with regard to washing efficiency and the chelation effect. The highest removal rates by soil washing (69% for Cu and 56% for Pb) were achieved at an HS concentration of 1,000 mg/L and soil:washing solution ratio of 1:25. Washing with HS was found to be effective when the pH value was higher than 8, which can be attributed to the increased chelation effect between HS and heavy metals at the high pH range. In contrast, the washing efficiency decreased markedly in the low pH range due to HS precipitation. The chelation capacities for Cu and Pb in the aqueous phase were determined to be 0.547mmol-Cu/g-HS and 0.192mmol-Pb/g-HS, respectively.

Properties of Extracellular Polyphenol Oxidase Isolated from Lentinus edodes JA01 (Lentinus edodes JA01에서 분리한 세포외 polyphenol oxidase의 부분적 성질에 관하여)

  • 신광수;김규중;홍순우;하영칠
    • Korean Journal of Microbiology
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    • v.24 no.2
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    • pp.141-146
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    • 1986
  • To find the role of polyphenol oxidase in lignin biodegradation, chracteristics of extracellular polyphenol oxidase activity from Lentinus edodes JA01 was investigated. Polyphenol oxidase had its optimum activity at pH 4.5 and $45^{\circ}C$ respectively. Also, the enzyme was very unstable in various pHs and comparatively heat stable up to $60^{\circ}C$. In $lignosulfonate-NH_4$ salts medium, the growth rate of L.edodes JA 01 was relatively slow and polyphenol oxidase activity appeared 2 and 14 days after inoculation. No significant relationships were found between polyphenol oxidase activity and the amounts of lignosulfonate present in the culture medium.

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