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Cytotoxic activities of alkaloid constituents from the climbing stems and rhizomes of Sinomenium acutum against cancer stem cells

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Abstract

From the methanolic extract of the climbing stems and rhizomes of Sinomenium acutum, two new aporphine analogues, acutumalkaloids I and II, were isolated together with fifteen known compounds including lysicamine. The chemical structures of the isolated new compounds were elucidated based on chemical/physicochemical evidence such as NMR and MS spectra. For acutumalkaloids I and II, the absolute configurations were established by comparison of experimental and predicted electronic circular dichroism (ECD) data. We compared anti-proliferative activities of isolated compounds with reported naturally occurring Wnt/β-catenin pathway inhibitor, nuciferine. Among the isolated compounds, we found lysicamine have anti-proliferative activity against both of HT-29 human colon cancer cell line and its cancer stem cells (CSCs). The IC50 values of lysicamine against non-CSCs and its CSCs were lower than that of nuciferine. In addition, the results of western blotting analysis suggested that lysicamine inhibited the expression of Wnt/β-catenin pathway target protein such as survivin. These results suggested that lysicamine show cytotoxic activity via inhibition of Wnt/β-catenin pathway.

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Acknowledgements

Not applicable.

Funding

This work was supported by JSPS KAKENHI Grant number JP20H03397.

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Authors and Affiliations

  1. Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, 607-8412, Japan

    Masaya Okayama, Takahiro Matsumoto, Takahiro Kitagawa, Seikou Nakamura & Tetsushi Watanabe

  2. Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki, 859-3298, Japan

    Tomoe Ohta & Tatsusada Yoshida

Authors
  1. Masaya Okayama
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  2. Takahiro Matsumoto
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  3. Takahiro Kitagawa
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  4. Seikou Nakamura
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  5. Tomoe Ohta
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  6. Tatsusada Yoshida
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  7. Tetsushi Watanabe
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Contributions

Conceptualization and project administration, TM; methodology, MO, TM, TO, and TY; investigation and formal analysis and data curation, MO, TM, TK, SN, TO, and TY; resources and software TM, SN, TY, and TW; writing–original draft preparation and visualization, MO and TM; writing–review and editing, supervision, and funding acquisition, TM, SN, and TW; All authors have read and agreed to the published version of the manuscript.

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Correspondence to Takahiro Matsumoto or Tetsushi Watanabe.

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11418_2023_1744_MOESM1_ESM.docx

The 1H, 13C, and 2D NMR spectra, optimized geometries, the minimum value of frequency, relative free-energies, and Boltzmann distributions of conformers for 1 and 3 are available free of charge via the Internet (DOCX 1589 KB)

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Okayama, M., Matsumoto, T., Kitagawa, T. et al. Cytotoxic activities of alkaloid constituents from the climbing stems and rhizomes of Sinomenium acutum against cancer stem cells. J Nat Med 78, 226–235 (2024). https://doi.org/10.1007/s11418-023-01744-4

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  • DOI: https://doi.org/10.1007/s11418-023-01744-4

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