Inhibition of human glioblastoma multiforme cells by 10,11-dehydrocurvularin through the MMP-2 and PI3K/AKT signaling
Hao Yan1, Zhenhao Fu2, Pingxin Lin1
1National Engineering Research Center for Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, 214122, China.
Abstract:
Glioblastoma, formerly known as glioblastoma multiforme (GBM), is a malignant nervous system tumor with high morbidity, recurrence rate, and mortality. Treating glioblastoma is difficult due to complicating factors, and novel therapeutic strategies are required to overcome resistance. In this study, we investigate the glioblastoma inhibitory activity of 10,11-dehydrocurvularin (DCV), a polyketide compound with broad biological activities, despite the fact that its anti-glioma properties and related mechanisms have yet to be studied. We look at how DCV affects glioblastoma cell lines U251 and U87 versus HEB cells. We discover that DCV inhibits glioblastoma cell proliferation, colony formation, migration, and invasion, as well as causing cell apoptosis. DCV treatment inhibits AKT phosphorylation and decreases the level of the PI3K/AKT pathway downstream protein MMP2. Our findings suggest that DCV could be a candidate for developing more potent glioblastoma chemotherapeutic drugs.
Insights
10,11-dehydrocurvularin (DCV) inhibits glioblastoma cell growth, migration, and invasion, and promotes apoptosis. This compound shows potential as a novel chemotherapeutic agent for glioblastoma treatment.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Pharmacology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis.
- Current treatments face challenges due to tumor resistance and recurrence.
- Novel therapeutic strategies are urgently needed for glioblastoma treatment.
Purpose of the Study:
- To investigate the anti-glioma activity of 10,11-dehydrocurvularin (DCV).
- To explore the underlying mechanisms of DCV's effect on glioblastoma cells.
Main Methods:
- Assessed DCV's impact on glioblastoma cell lines (U251, U87) versus normal human epidermal cells (HEB).
- Evaluated effects on cell proliferation, colony formation, migration, invasion, and apoptosis.
- Analyzed DCV's influence on the PI3K/AKT pathway, including AKT phosphorylation and MMP2 levels.
Main Results:
- DCV significantly inhibited glioblastoma cell proliferation, colony formation, migration, and invasion.
- DCV treatment induced apoptosis in glioblastoma cells.
- DCV suppressed AKT phosphorylation and reduced matrix metalloproteinase-2 (MMP2) levels, a downstream target of the PI3K/AKT pathway.
Conclusions:
- 10,11-dehydrocurvularin (DCV) exhibits potent anti-glioblastoma properties.
- DCV's mechanism involves the inhibition of the PI3K/AKT signaling pathway.
- DCV represents a promising candidate for the development of new glioblastoma chemotherapeutic drugs.
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