KSRP/FUBP2 Is a Binding Protein of GO-Y086, a Cytotoxic Curcumin Analogue

Yamakoshi, Hiroyuki; Kanoh, Naoki; Kudo, Chiaki; Sato, Atsuko; Ueda, Kazunori; Muroi, Makoto; Kon, Shunsuke; Satake, Masanobu; Ohori, Hisatsugu; Ishioka, Chikashi; Oshima, Yoshiteru; Osada, Hiroyuki; Chiba, Natsuko; Shibata, Hiroyuki; Iwabuchi, Yoshiharu

doi:10.1021/ml1000454

Cited by 20 publications

(17 citation statements)

References 22 publications

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“…Curcumin analogue (GO-Y086) is able to bind with nuclear protein KSRP by covalent modification and markedly suppresses c-Myc protein expression. GO-Y086 has been studied for the control of c-Myc expression in colon cancer cell lines (HCT116) ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma

Pruksakorn

Teeyakasem

Klangjorhor

et al. 2016

International Journal of Oncology

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Osteosarcoma is a common malignant bone tumor in children and adolescents. The current 5-year survival rate is ~60% and that seems to be reaching a plateau. In order to improve treatment outcomes of osteosarcoma, a better understanding of tumorigenesis and underlying molecular mechanisms is required for searching out possible new treatment targets. This study aimed to identify the potential proteins involving the pathogenesis of osteosarcoma using a proteomics approach. Proteins extracted from primary cell culture of osteosarcoma (n=7) and osteoblasts of cancellous bone (n=7) were studied. Using 2-DE based proteomics and LC-MS/MS analysis, we successfully determined seven differentially expressed protein spots. Four upregulated proteins and three downregulated proteins were observed in this study in which KH-type splicing regulatory protein (KSRP) was selected for further exploration. KSRP was significantly upregulated in osteosarcoma cells compared to osteoblasts using western blot assay. In addition, immunohistochemistry demonstrated that KSRP was also highly expressed in osteosarcoma tissue of independent cases from the experimental group. More importantly, KSRP silencing of osteosarcoma cell lines significantly decreased cell proliferation, migration ability, as well as implantation and growth ability in chick chorioallantoic membrane assay. Taken together, these findings demonstrate, that KSRP plays important roles in regulatory controls of osteosarcoma pathogenesis and serves as a potentially therapeutic target of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma

Pruksakorn

Teeyakasem

Klangjorhor

et al. 2016

International Journal of Oncology

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“…Our DCA bearing the same chemical structure can directly bind KH type‐splicing regulatory protein, which is a single‐strand nucleic acid binding protein that affects different species of mRNAs and microRNAs. Preliminary data indicated that GO‐Y078 affects microRNAs, some of which are associated with the regulation of fibronectin expression.…”

Section: Discussionmentioning

confidence: 99%

Curcumin analog, GO‐Y078, overcomes resistance to tumor angiogenesis inhibitors

Shimazu

Inoue

Sugiyama³

et al. 2018

Cancer Science

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Tumor angiogenesis inhibition is one of the most potent strategies in cancer chemotherapy. From past clinical studies, inhibition of the vascular endothelial growth factor pathway successfully treats malignant tumors. However, vascular endothelial growth factor inhibitors alone cannot cure tumors. Moreover, resistance to small molecule inhibitors has also been reported. Herein, we show the antiangiogenic potential of a newly synthesized curcumin analog, GO‐Y078, that possibly functions through inhibition of actin stress fiber formation, resulting in mobility inhibition; this mechanism is different from that of vascular endothelial growth factor inhibition. In addition, we examined the detailed mechanism of action of the antiangiogenesis potential of GO‐Y078 using human umbilical venous epithelial cells resistant to angiogenesis inhibitors (HUVEC‐R). GO‐Y078 inhibited the growth and mobility of HUVEC‐R at 0.75 μmol/L concentration. Expression analyses by microarray and RT‐PCR showed that expressions of genes including that of fibronectin 1 were significantly suppressed. Among these genes, fibronectin 1 is abundantly expressed and, therefore, seems to be a good target for GO‐Y078. In a knockdown experiment using Si‐oligo of fibronectin 1 (FN1), FN1 expression was decreased to half of that in mock experiments as well as GO‐Y078. Knockdown of FN1 resulted in the suppression of HUVEC‐R growth at 24 hours after treatment. Fibronectin is a key molecule contributing to angiogenesis that could be inhibited by GO‐Y078. Thus, resistance to vascular endothelial growth factor inhibition can be overcome using GO‐Y078.

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“…All solvents and chemicals used here were obtained as reagent‐grade quality from commercial suppliers and used without further purification. 2‐(4‐Phenylphenoxy)ethanol (BP‐C2‐OH) and 6‐(4‐phenylphenoxy)hexanol (BP‐C6‐OH) were prepared by similar literature procedure of 2‐phenylethanol. Octakis(propenyl succinicanhydrido)polyhedral octasilicate (OS‐SA) was prepared using a literature method .…”

Section: Methodsmentioning

confidence: 99%

Syntheses of biphenyl‐terminated polyhedral oligomeric octasilicate‐core dendrimers and their single‐component optical transparent free‐standing thermoplastic films

Irie

Naka

2015

J. Polym. Sci. Part A: Polym. Chem.

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2‐Biphenylethyl and 2‐biphenylhexyl‐terminated polyhedral oligomeric octasilicate (OS)‐core polyester‐typed dendrimers, denoted as OS‐C2‐BP and OS‐C6‐BP, respectively, were prepared by ring‐opening reaction and subsequent condensation of octakis(propenyl succinicanhydrido)polyhedral octasilicate (OS‐SA) with 2‐(4‐phenylphenoxy)ethanol (BP‐C2‐OH) and 6‐(4‐phenylphenoxy)hexanol (BP‐C6‐OH), respectively. OS‐C2‐BP formed a transparent film, whereas OS‐C6‐BP formed an opaque whitish waxy film. The coating film of OS‐C2‐BP was easily peeled off from a substrate and formed a free‐standing film. The results of X‐ray diffraction and differential scanning calorimeter suggest that the film of OS‐C2‐BP was amorphous, whereas OS‐C6‐BP contained crystalline domains. Thermogravimetric analysis of OS‐C2‐BP and OS‐C6‐BP showed 5 wt % weight losses at 362 °C and 283 °C, respectively. OS‐C2‐BP offered higher thermal resistance than OS‐C6‐BP. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1437–1443

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KSRP/FUBP2 Is a Binding Protein of GO-Y086, a Cytotoxic Curcumin Analogue

Cited by 20 publications

References 22 publications

Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma

Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma

Curcumin analog, GO‐Y078, overcomes resistance to tumor angiogenesis inhibitors

Syntheses of biphenyl‐terminated polyhedral oligomeric octasilicate‐core dendrimers and their single‐component optical transparent free‐standing thermoplastic films

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