Beta-Caryophyllene Augments Radiotherapy Efficacy in GBM by Modulating Cell Apoptosis and DNA Damage Repair via PPARγ...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Glioblastoma multiforme (GBM) is an aggressive brain cancer with poor treatment outcomes, often due to radioresistance.
• Radiotherapy (RT) is a standard treatment, but its efficacy is limited by GBM's resistance.
• Developing effective radiosensitizers is crucial to improve GBM treatment response.

Purpose of the Study:

• To investigate the potential of beta-caryophyllene (BCP), a natural cannabinoid, as a radiosensitizer for GBM.
• To evaluate the combined effects of BCP and RT on GBM cells and a tumor model.
• To elucidate the molecular mechanisms underlying BCP's radiosensitizing effects.

Main Methods:

• Utilized U87MG and GL261 GBM cell lines and a GL261 tumor-bearing mouse model.
• Assessed treatment efficacy using MTT assays and tumor growth tracking.
• Investigated molecular mechanisms via western blotting, immunofluorescence, and DNA damage assays (γH2AX).

Main Results:

• BCP synergistically enhanced RT efficacy in GBM cells, confirmed by combination index analysis.
• BCP treatment led to delayed DNA damage repair, sustained γH2AX signals, and upregulated PPARγ.
• BCP inhibited survival pathways (pAKT, pERK, NF-κB) and significantly reduced tumor growth in vivo with no observed side effects.

Conclusions:

• Beta-caryophyllene acts as a potent radiosensitizer for glioblastoma multiforme.
• BCP enhances RT efficacy by inhibiting DNA repair, inducing apoptosis, and suppressing pro-survival signaling.
• BCP demonstrates significant therapeutic potential for improving glioblastoma radiotherapy outcomes.