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Article

Lignin Isolated by Microwave-Assisted Acid-Catalyzed Solvolysis Induced Cell Death in Mammalian Tumor Cells by Modulating Apoptotic Pathways

by
Rio Kashimoto
1,
Eriko Ohgitani
1,
Yutaka Makimura
2,
Tatsuya Miyazaki
2,
Chihiro Kimura
2,
Masaharu Shin-Ya
1,
Hiroshi Nishimura
2,
Giuseppe Pezzotti
1,3,
Takashi Watanabe
2,* and
Osam Mazda
1,*
1
Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
2
Laboratory of Biomass Conversion, Research Institute for Sustainable Humanosphere (RISH), Kyoto University, Uji 611-0011, Japan
3
Ceramic Physics Laboratory, Kyoto Institute of Technology, Kyoto 611-0011, Japan
*
Authors to whom correspondence should be addressed.
Molecules 2024, 29(23), 5490; https://doi.org/10.3390/molecules29235490
Submission received: 30 August 2024 / Revised: 28 October 2024 / Accepted: 14 November 2024 / Published: 21 November 2024
(This article belongs to the Special Issue Natural Products in Anticancer Activity: 2nd Edition)
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Abstract

Lignin, the most abundant renewable aromatic polymer, has been shown to suppress the growth of mammalian tumor cells. Despite extensive studies on lignin structure and its engineering, there is little information on the biological activity of lignin in relation to its molecular structure or the molecular mechanisms by which lignin suppresses tumor cells in mammalian species. Here, we prepared microwave-assisted acid-catalyzed solvolysis lignin (MASL) from Japanese cedar and Eucalyptus globulus and assessed its effects on human and mouse tumor cells. SEC indicated that MASL consists of oligomeric aromatics from the woody plants. Our data showed that MASL significantly reduced the viability of tumor cells by modulating apoptotic pathways. MASL treatment upregulated TNF-α, Fas, and FasL expression levels, while suppressing anti-apoptotic NF-κB and mTOR pathways in tumor cells. In vivo experiments were also performed using tumor-bearing mice to confirm the anti-tumor effects of MASL. Repetitive administrations of a MASL (YM CL1T) significantly inhibited tumor growth in mice in association with elevation of caspase 3 expression. These findings strongly suggest the potential usefulness of low-molecular-weight lignin as an effective therapeutic against malignancies.
Keywords: lignin; apoptosis; cancer therapy; biomass conversion; TNF-α; NF-κB p65; mTOR; caspase 3 lignin; apoptosis; cancer therapy; biomass conversion; TNF-α; NF-κB p65; mTOR; caspase 3
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MDPI and ACS Style

Kashimoto, R.; Ohgitani, E.; Makimura, Y.; Miyazaki, T.; Kimura, C.; Shin-Ya, M.; Nishimura, H.; Pezzotti, G.; Watanabe, T.; Mazda, O. Lignin Isolated by Microwave-Assisted Acid-Catalyzed Solvolysis Induced Cell Death in Mammalian Tumor Cells by Modulating Apoptotic Pathways. Molecules 2024, 29, 5490. https://doi.org/10.3390/molecules29235490

AMA Style

Kashimoto R, Ohgitani E, Makimura Y, Miyazaki T, Kimura C, Shin-Ya M, Nishimura H, Pezzotti G, Watanabe T, Mazda O. Lignin Isolated by Microwave-Assisted Acid-Catalyzed Solvolysis Induced Cell Death in Mammalian Tumor Cells by Modulating Apoptotic Pathways. Molecules. 2024; 29(23):5490. https://doi.org/10.3390/molecules29235490

Chicago/Turabian Style

Kashimoto, Rio, Eriko Ohgitani, Yutaka Makimura, Tatsuya Miyazaki, Chihiro Kimura, Masaharu Shin-Ya, Hiroshi Nishimura, Giuseppe Pezzotti, Takashi Watanabe, and Osam Mazda. 2024. "Lignin Isolated by Microwave-Assisted Acid-Catalyzed Solvolysis Induced Cell Death in Mammalian Tumor Cells by Modulating Apoptotic Pathways" Molecules 29, no. 23: 5490. https://doi.org/10.3390/molecules29235490

APA Style

Kashimoto, R., Ohgitani, E., Makimura, Y., Miyazaki, T., Kimura, C., Shin-Ya, M., Nishimura, H., Pezzotti, G., Watanabe, T., & Mazda, O. (2024). Lignin Isolated by Microwave-Assisted Acid-Catalyzed Solvolysis Induced Cell Death in Mammalian Tumor Cells by Modulating Apoptotic Pathways. Molecules, 29(23), 5490. https://doi.org/10.3390/molecules29235490

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