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Naringenin Sensitizes Resistant C6 Glioma Cells with a Repressive Impact on the Migrating Ability
Jayalakshmi J1, Arambakkam Janardhanam Vanisree1
1Department of Biochemistry, University of Madras, Chennai, Tamil Nadu, India.
Background:
Glioma, the most common form of a malignant brain tumour is characterised by a poor prognosis, which is attributable to its resistance against current therapeutic approaches. Temozolomide (TMZ), a DNA alkylating agent, is the first-line drug for glioma treatment. Long-term treatment using TMZ was reported to culminate in the development of resistance with overexpression of multidrug resistance 1 gene coded protein P-glycoprotein, which in turn releases the drugs from the tumour cells.
Purpose:
Thus, to circumvent such resistance issues, the current study attempted to explore the effect of naringenin (a flavanone) with proven antiglial tumour potential, in mitigating the features of TMZ resistance.
Methods:
Colony-forming assay, invasion assay and scratch wound assay were performed among the groups, namely tumour control (C6), vehicle control (V), naringenin (NGEN)-treated, drug-resistant tumour cells (C6R), and drug resistance cells added with NGEN (C6R+NGEN), to examine the impact of NGEN on migration and invasion. The effect of NGEN on filopodia length and density during cell migration was also studied in addition to the matrix metalloproteinases (MMP-2 and MMP-9) and p-ERK levels.
Results And Conclusion:
NGEN and C6R+NGEN groups had shown significant reduction (P < .01) in length and density of filopodia, colony formation, invasion and wound healing. Further, NGEN could also modify the assessed protein levels (P < .001), which were involved in migration and invasion in sensitive and resistant cells. Our study had provided the first evidence on NGEN-induced enhanced sensitivity against TMZ resistance with profound influence as an antimigratory and anti-invasive agent.
Insights
Naringenin (NGEN) enhances temozolomide (TMZ) sensitivity in glioma by reducing cell migration and invasion. This flavanone offers a potential strategy to overcome drug resistance in brain tumors.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Glioma, a common malignant brain tumor, exhibits poor prognosis due to therapeutic resistance.
- Temozolomide (TMZ) is a primary glioma treatment, but resistance develops through mechanisms like P-glycoprotein overexpression.
- This resistance limits the long-term efficacy of standard chemotherapy.
Purpose of the Study:
- To investigate naringenin's (NGEN) potential in overcoming temozolomide (TMZ) resistance in glioma.
- To evaluate NGEN's effect on mitigating drug resistance features.
- To explore NGEN as a sensitizer for TMZ-resistant glioma.
Main Methods:
- Cellular assays including colony formation, invasion, and scratch wound assays were employed.
- Effects of NGEN on cell migration, filopodia dynamics, matrix metalloproteinases (MMP-2, MMP-9), and p-ERK levels were assessed.
- Experiments involved glioma cells (C6), drug-resistant cells (C6R), and treatments with NGEN and TMZ.
Main Results:
- Naringenin significantly reduced filopodia length/density, colony formation, invasion, and wound healing in both sensitive and resistant cells.
- NGEN treatment led to significant modifications in protein levels associated with migration and invasion.
- A notable decrease in cell migration and invasion was observed in NGEN-treated groups.
Conclusions:
- Naringenin (NGEN) demonstrates significant potential in enhancing sensitivity to temozolomide (TMZ) in resistant glioma cells.
- NGEN acts as a potent antimigratory and anti-invasive agent, offering a novel therapeutic avenue.
- This study provides the first evidence of NGEN's role in overcoming TMZ resistance in glioma.
