| Description: |
Isolinderalactone shows anti-inflammatory and anticancer capacity, it induces apoptosis in MDA-MB-231 cells and suppresses STAT3 signaling pathway through regulation of SOCS3 and miR-30c, may become a novel treatment for triple-negative breast cancer in the future; it exhibits moderate iNOS inhibitory activity, with the IC50 value of 0.30 uM. |
| Targets: |
p21 | NOS | Caspase | STAT | SOCS3 | miR-30c |
| In vitro: |
| J Nat Prod. 2011 Dec 27;74(12):2489-96. | | Secondary metabolites from the roots of Neolitsea daibuensis and their anti-inflammatory activity.[Pubmed: 22148193] | Bioassay-guided fractionation of the roots of Neolitsea daibuensis afforded three new β-carboline alkaloids, daibucarbolines A-C (1-3), three new sesquiterpenoids, daibulactones A and B (4 and 5) and daibuoxide (6), and 20 known compounds.
METHODS AND RESULTS:
The structures of 1-6 were determined by spectroscopic analysis and single-crystal X-ray diffraction. Daibucarboline A (1), Isolinderalactone (7), 7-O-methylnaringenin (8), and prunetin (9) exhibited moderate iNOS inhibitory activity, with IC₅₀ values of 18.41, 0.30, 19.55, and 10.50 μM, respectively. | | Oncol Rep. 2016 Mar;35(3):1356-64. | | Isolinderalactone enhances the inhibition of SOCS3 on STAT3 activity by decreasing miR-30c in breast cancer.[Pubmed: 26707189] | Development of an efficient treatment for triple-negative breast cancer is an urgent issues. Compounds from plant extracts are a potential source of novel cancer treatment. Isolinderalactone, a kind of sesquiterpenoids compound, was purified from the root of Lindera strychnifolia and Neolitsea daibuensis and shows anti-inflammatory and anticancer capacity.
METHODS AND RESULTS:
In the present study, Isolinderalactone induced apoptosis in MDA-MB-231 cells which is a kind of triple-negative breast cancer cell line through induction of an intrinsic mitochondria-mediated and caspase-independent cell death. Treatment of Isolinderalactone increased the protein level of the suppressor of cytokine signaling 3 (SCOS3), decreased phosphorylation of the signal transducer and activator of transcription 3 (STAT3), and suppressed expression of the down-stream genes of the X-linked inhibitor of apoptosis protein in MDA-MB-231 cells. Our results further showed that the level of SOCS3 expression was induced by Isolinderalactone due to inhibiting the microRNA hsa-miR-30c-5p (miR-30c) expression. In addition, intraperitoneal injection of Isolinderalactone induced apoptosis in a xenograft breast tumor while it did not significantly affect the histology of liver, kidney and lung of the treated mice.
CONCLUSIONS:
In conclusion, Isolinderalactone induces apoptosis in MDA-MB‑231 cells and suppresses STAT3 signaling pathway through regulation of SOCS3 and miR-30c. It may become a novel treatment for triple-negative breast cancer in the future. |
|
| In vivo: |
| Cancer Lett . 2020 May 28;478:71-81 | | Isolinderalactone suppresses human glioblastoma growth and angiogenic activity in 3D microfluidic chip and in vivo mouse models[Pubmed: 32173479] | | Abstract
Glioblastoma multiforme (GBM) is a lethal and highly vascular type of brain tumor. We previously reported that Isolinderalactone enhances GBM apoptosis in vitro and in vivo, but its role in tumor angiogenesis is unknown. Here, we investigated the anti-angiogenic activity of Isolinderalactone and its mechanisms. In a human GBM xenograft mouse model, Isolinderalactone significantly reduced tumor growth and vessels. Isolinderalactone decreased the expression of vascular endothelial growth factor (VEGF) mRNA, protein, and VEGF secretion in hypoxic U-87 GBM cells and also in xenograft GMB tissue. In addition, we demonstrated that Isolinderalactone significantly inhibited the proliferation, migration, and capillary-like tube formation of human brain microvascular endothelial cells (HBMECs) in the presence of VEGF. We also found that Isolinderalactone decreased sprout diameter and length in a 3D microfluidic chip, and strongly reduced VEGF-triggered angiogenesis in vivo Matrigel plug assay. Isolinderalactone downregulated hypoxia-inducible factor-1α (HIF-1α) and HIF-2α proteins, decreased luciferase activity driven by the VEGF promoter in U-87 cells under hypoxic conditions, and suppressed VEGF-driven phosphorylation of VEGFR2 in HBMECs. Taken together, our results suggest that Isolinderalactone is a promising candidate for GBM treatment through tumor angiogenesis inhibition.
Keywords: 3D microfluidic chip; Angiogenesis; Brain tumor; Hypoxia-inducible factor; Vascular endothelial growth factor. |
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