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Cited by 21Glioma Diagnosis and TreatmentPhytochemical compounds biological activitiesNatural product bioactivities and synthesis

Mechanisms involved in the anti-tumor effects of Toosendanin in glioma cells

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Zhang, Chaochao, Gao, Haijun, Liu, Ziqiang, Lai, Jiacheng, Zhan, Zhixin, Chen, Yong, Huang, Haiyan·2021·Cancer Cell International
DOI 10.1186/s12935-021-02186-2PMC PMC8444588
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Abstract

Background: Toosendanin (TSN) is a triterpenoid compound mainly used as an ascaris repellant. Recent studies have shown that it possesses antitumor effects in many types of tumor cells. However, the effects of TSN on glioma cells have rarely been reported. Methods: Different assays were performed to investigate the effects of TSN on the different glioma cell lines including U87MG and LN18. The assays included colony formation, wound healing, and transwell assays. Furthermore, Hoechst 33342 staining, flow cytometry, and western blotting analysis were performed to investigate the apoptotic activities of TSN. Finally, the results were confirmed using a xenograft tumor model that comprised of nude mice. Results: In vitro, the CCK-8 and colony formation assays showed that TSN effectively inhibited glioma cell proliferation. Moreover, the inhibitory effects on glioma cell migration and invasion were demonstrated through the wound healing and transwell assays, respectively. Hoechst 33342 staining, flow cytometry, and western blotting assays demonstrated the significant effect of TSN in the apoptosis induction of glioma cells. Furthermore, the anti-glioma effect of TSN was exerted through the inhibition of the PI3K/Akt/mTOR signaling pathways as demonstrated by western blotting analysis. In addition, the effects of TSN on glioma cell viability, apoptosis, cell cycle arrest, migration, and invasion were reversed by 740Y-P, a PI3K activator. Finally, the mouse xenograft model confirmed the suppressive effect of TSN on tumor growth in vivo. Conclusion: Our results suggest that TSN is a promising chemotherapeutic drug for patients with glioma.

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  • TSN possesses antitumor effects in various cancers by regulating c-Myc, PI3K/AKT/mTOR, and NF-κB, which are strongly correlated with STAT3.

    “Recent studies have shown that TSN possesses antitumor effects in various cancers, such as triple-negative breast cancer (TNBC), glioma, ovarian cancer, liver cancer, CRC, by regulating c-Myc, PI3K/AKT/mTOR, and NF-κB, which are strongly correlated with STAT3 (52–55).”

    From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [53]

    The Results section reports that TSN inhibited PI3K/Akt/mTOR signaling in glioma cells, and the Discussion notes reports of antitumor effects in other malignancies. This paper does not establish that TSN acts through c-Myc or NF-κB, or that the mechanisms claimed are strongly correlated with STAT3. (LLM, conf=0.89)

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Authors
Zhang, C., Gao, H., Liu, Z., Lai, J., Zhan, Z., Chen, Y., & Huang, H.
Affiliations
First Hospital of Jilin University (CN)
Corresponding author
  • Chen, Yong
  • Huang, Haiyan
ORCID
Venue
Cancer Cell International
Publisher
Springer Science and Business Media LLC
Published
2021-09-16
Volume
21
Issue
1
Pages
492-492
ISSN
1475-2867 (ISSN-L)
DOI
10.1186/s12935-021-02186-2
PMC
PMC8444588
OpenAlex
W3171729349
Cited by
21
References
46
Citations by year
2026: 2 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 6
FWCI
1.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Cell International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • jilin provincial science research fund (20180101158JC, 20200201613JC)
  • the 13th five-year plan of jilin provincial department of education (JJKH20180191KJ)
  • the interdisciplinary innovation project of the first hospital of jilin university (JDYYJC001)
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical compounds biological activities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
Keywords
toosendanin, glioma, triterpenoids, anticancer activity, apoptosis, cell proliferation inhibition, cell migration and invasion, PI3K/AKT/mTOR pathway, 740Y-P, xenograft tumor model, U87MG

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