Dataset Information

Liposomal honokiol inhibits glioblastoma growth through regulating macrophage polarization.

ABSTRACT:

Background

Glioblastoma is a type of aggressive brain tumor-related to infiltrating microglia/macrophages. Various studies have identified antitumor properties of a bioactive plant compound named honokiol, originating from the Magnolia species. This beneficial characteristic of honokiol has been discovered in many malignant tumors.

Methods

We investigated the molecular mechanisms behind the anti-glioma effects of liposomal honokiol (Lip-HNK) using qRT-PCR, Western blot, co-culture, and in vivo animal experiments.

Results

It was discovered that the expression of M1 markers such as CD11c, inducible nitric oxide synthase (iNOS), and major histocompatibility complex (MHC) II (IA/IE subregions) induced by lipopolysaccharide (LPS)/IFN-γ was increased by Lip-HNK, and M2 markers Arg1 and CD206 induced by interleukin (IL)-4 had reduced expression, thus inhibiting tumor cell growth through co-culture experiments. After Lip-HNK treatment, a considerable increase in signal transducer and activator of transcription 1 (STAT1) activation was observed, and in contrast, STAT6 activation was suppressed. STAT1 and STAT6 are the key signaling molecules mediating M1 and M2 polarization, respectively. Furthermore, the percentage of CD11c-positive M1 macrophages was increased by Lip-HNK in G422 xenograft mice, while Lip-HNK treatment reduced the CD206-positive M2 macrophage distribution in tumor tissues. These findings are consistent with the decline in tumor volume seen in mice treated with Lip-HNK.

Conclusions

Lip-HNK inhibits the growth of glioblastoma by upregulating M1 macrophages and limiting M2 phenotypic macrophages.

SUBMITTER: Li S

PROVIDER: S-EPMC8667111 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Liposomal honokiol inhibits glioblastoma growth through regulating macrophage polarization.

Li Shenglan S Li Long L Chen Jinyi J Fan Yaqiong Y Wang Ce C Du Yuan Y Guo Caixia C Chen Feng F Li Wenbin W

Annals of translational medicine 20211101 22

<h4>Background</h4>Glioblastoma is a type of aggressive brain tumor-related to infiltrating microglia/macrophages. Various studies have identified antitumor properties of a bioactive plant compound named honokiol, originating from the <i>Magnolia species</i>. This beneficial characteristic of honokiol has been discovered in many malignant tumors.<h4>Methods</h4>We investigated the molecular mechanisms behind the anti-glioma effects of liposomal honokiol (Lip-HNK) using qRT-PCR, Western blot, co- ...[more]

PMID: 34988153

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Project description:BackgroundLycorine has been revealed to inhibit the development of many kinds of malignant tumors, including glioblastoma multiforme (GBM). Although compelling evidences demonstrated Lycorine's inhibition on cancers through some peripheral mechanism, in-depth mechanism studies of Lycotine's anti-GBM effects still call for further exploration. Epidermal Growth Factor Receptor (EGFR) gene amplification and mutations are the most common oncogenic events in GBM. Targeting EGFR by small molecular inhibitors is a rational strategy for GBM treatment.MethodsThe molecular docking modeling and in vitro EGFR kinase activity system were employed to identify the potential inhibitory effects of Lycorine on EGFR. And the Biacore assay was used to confirm the direct binding status between Lycorine and the intracellular EGFR (696-1022) domain. In vitro assays were conducted to test the suppression of Lycorine on the biological behavior of GBM cells. By RNA interference, EGFR expression was reduced then cells underwent proliferation assay to investigate whether Lycorine's inhibition on GBM cells was EGFR-dependent or not. RT-PCR and western blotting analysis were carried out to investigate the underlined molecular mechanism that Lycorine exerted on EGFR itself and EGFR signaling pathway. Three different xenograft models (an U251-luc intracranially orthotopic transplantation model, an EGFR stably knockdown U251 subcutaneous xenograft model and a patient-derived xenograft model) were performed to verify Lycorine's therapeutic potential on GBM in vivo.ResultsWe identified a novel small natural molecule Lycorine binding to the intracellular EGFR (696-1022) domain as an inhibitor of EGFR. Lycorine decreased GBM cell proliferation, migration and colony formation by inducing cell apoptosis in an EGFR-mediated manner. Furthermore, Lycorine inhibited the xenograft tumor growths in three animal models in vivo. Besides, Lycorine impaired the phosphorylation of EGFR, AKT, which were mechanistically associated with expression alteration of a series of cell survival and death regulators and metastasis-related MMP9 protein.ConclusionsOur findings identify Lycorine directly interacts with EGFR and inhibits EGFR activation. The most significant result is that Lycorine displays satisfactory therapeutic effect in our patient-derived GBM tumor xenograft, thus supporting the conclusion that Lycorine may be considered as a promising candidate in clinical therapy for GBM.

Dataset Information

Liposomal honokiol inhibits glioblastoma growth through regulating macrophage polarization.

Background

Methods

Results

Conclusions

Publications

Liposomal honokiol inhibits glioblastoma growth through regulating macrophage polarization.

Similar Datasets

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