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Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor.
- Source :
- Cancers; Jan2019, Vol. 11 Issue 1, p22, 1p
- Publication Year :
- 2019
-
Abstract
- Malignant gliomas are the most aggressive forms of brain tumors; whose metastasis and recurrence contribute to high rates of morbidity and mortality. Glioma stem cell-like cells are a subpopulation of tumor-initiating cells responsible for glioma tumorigenesis, metastasis, recurrence and resistance to therapy. Epidermal growth factor receptor (EGFR) has been reported to be dysregulated in most cancers, including gliomas and its functions are closely linked to initiating tumor metastasis and a very poor prognosis. In search for compounds that may reduce the tumorigenic potential of gliomas/glioblastomas honokiol attracted our attention. Honokiol, purified from the bark of traditional Chinese herbal medicine Magnolia species, is beneficial in vitro and in animal models via a variety of pharmacological effects, including anti-inflammatory, anti-angiogenetic, anti-arrhythmic and antioxidant activities, as well as anti-proliferative and proapoptotic effects in a wide range of human cancer cells. However, its effects on glioma cells are unknown. Here, we used different concentrations of honokiol in treating U251 and U-87 MG human glioma/glioblastoma cells in cell culture. Results showed that honokiol inhibited glioma cell viability and colony formation and promoted apoptosis. It also inhibited glioma cell migration/proliferation and invasion. In addition, honokiol promoted apoptosis and reduced Bcl-2 expression, accompanied by increase in Bax expression. Honokiol reduced expression of EGFR, CD133 and Nestin. Moreover, honokiol inhibited the activation of both AKT and ERK signaling pathways, increased active caspase-3 level and reduced phosphorylation of STAT3. U-87 MG xenografts in nude mice and in immunotolerant zebrafish yolk sac showed that honokiol inhibits tumor growth and metastasis. Altogether, results indicate that honokiol reduces tumorigenic potentials, suggesting hopes for honokiol to be useful in the clinical management of glioma/glioblastoma. [ABSTRACT FROM AUTHOR]
- Subjects :
- CELL proliferation
ANIMAL experimentation
ANTIGENS
APOPTOSIS
CARRIER proteins
CELL motility
CELLULAR signal transduction
CYTOSKELETAL proteins
EPIDERMAL growth factor
FISHES
GENE expression
GLIOMAS
CHINESE medicine
METASTASIS
MICE
ONCOGENES
PHOSPHORYLATION
PROTEIN kinases
STEM cells
TRANSFERASES
PLANT extracts
CASPASES
CELL survival
IN vitro studies
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 11
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 134329237
- Full Text :
- https://doi.org/10.3390/cancers11010022