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Journal of Natural Medicines
Erschienen in:

24.01.2024 | Original Paper

Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7

verfasst von: Takahiro Kitagawa, Takahiro Matsumoto, Tomoe Ohta, Tatsusada Yoshida, Youhei Saito, Yuji Nakayama, Yuki Hadate, Eishi Ashihara, Tetsushi Watanabe

Erschienen in: Journal of Natural Medicines | Ausgabe 2/2024

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Abstract

The Wnt/β-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/β-catenin signaling pathway, named LPD-01 (1), and 1 inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that 1 inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of 1 in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/β-catenin signaling pathway-related proteins. As a result, 1 inhibited the expression of target proteins of Wnt/β-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (β-catenin) was not decreased, suggesting that 1 inhibited the Wnt/β-catenin signaling pathway without affecting β-catenin. Next, we investigated the target proteins of 1 using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that 1 directly binds to importin7. As expected, 1 inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-β-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/β-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of 1 for inhibition of the Wnt/β-catenin signaling pathway.

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Metadaten
Titel
Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7
verfasst von
Takahiro Kitagawa
Takahiro Matsumoto
Tomoe Ohta
Tatsusada Yoshida
Youhei Saito
Yuji Nakayama
Yuki Hadate
Eishi Ashihara
Tetsushi Watanabe
Publikationsdatum
24.01.2024
Verlag
Springer Nature Singapore
Erschienen in
Journal of Natural Medicines / Ausgabe 2/2024
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-023-01774-y

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