Study: CBD Kills Rare Ovarian Tumor Cells by Targeting TRPV2 Channel and Mitochondrial Pathway
- The study reveals that cannabidiol (CBD) can kill cells from granulosa cell tumors (GCTs), a rare ovarian cancer, by targeting a specific ion channel and mitochondrial pathway.
- Researchers found that 95% of GCT samples express the TRPV2 ion channel, which regulates cell size, proliferation, migration, hormone production, and the proteome of tumor cells.
- CBD-induced cell death in tumor cells primarily occurs through activation of TRPV2, but mitochondrial protein VDAC1 and the mitochondrial permeability transition pore (mPTP) also play crucial roles.
- TRPV2 may serve as a novel biomarker for GCT subtypes and represents a promising therapeutic target alongside its associated mitochondrial pathways.
A new study reports that cannabidiol (CBD), a non-intoxicating component of marijuana, may exploit a specific ion channel and a mitochondrial pathway to kill cells from a rare type of ovarian tumor. Published in Cell Communication and Signaling, the research was led by scientists at Ludwig Maximilian University and focused on granulosa cell tumors (GCTs), an uncommon ovarian cancer that currently lacks reliable markers and targeted treatments. The team examined tumor samples from 63 patients and a human granulosa tumor–derived cell line known as KGN.
Researchers found that 95% of GCT samples expressed the transient receptor potential vanilloid 2 (TRPV2) channel. Using CRISPR/Cas9 gene editing to delete TRPV2 in KGN cells, they observed larger cell size along with increased proliferation, migration and macropinocytosis. TRPV2 loss also altered steroid hormone production and changed the overall proteome of the cells, pointing to a broad regulatory role.
When exposed to CBD, normal KGN cells underwent rapid, dose- and time-dependent cell death. Cells lacking TRPV2 were noticeably more resistant, indicating that direct activation of TRPV2 is a key route for CBD’s toxic effect on these tumor cells. However, cell death was not fully blocked, prompting the team to map the TRPV2 interactome.
That analysis highlighted voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein involved in forming and sustaining the mitochondrial permeability transition pore (mPTP), as another CBD target linked to cell death. Blocking mPTP formation with cyclosporin A significantly reduced CBD-induced toxicity, and TRPV2-deficient cells treated with cyclosporin A became almost completely insensitive to CBD.
The authors conclude that TRPV2 expression could serve as a new marker to distinguish GCT subtypes and that TRPV2 itself, along with its associated pathways, represents a promising drug target for this rare ovarian cancer.