Cannabidiol (CBD) triggered programmed cell death and disrupted cell-cycle progression in human fibrosarcoma cells, according to a study published online by the Journal of Cannabis Research. Fibrosarcoma is a rare and aggressive cancer that develops in fibrous connective tissue and can be difficult to treat once it becomes advanced or metastatic.

For the study, researchers from the University of Cape Town and the South African Medical Research Council examined CBD’s effects on HT1080 human fibrosarcoma cells and noncancerous human skin fibroblasts.

The study focused partly on FAM111B, a protein associated with cancer-cell survival and proliferation. Previous research has found elevated levels of FAM111B in fibrosarcoma cells, with reductions in the protein associated with decreased cancer-cell growth and increased apoptosis, the process through which damaged or abnormal cells undergo programmed death.

Cells were exposed to varying concentrations of CBD for 24 hours. CBD reduced metabolic activity in both the cancerous and noncancerous cells in a dose-dependent manner, producing similar half-maximal inhibitory concentrations of 28.95 micromoles in fibrosarcoma cells and 30.75 micromoles in noncancerous fibroblasts.

The researchers said this result showed CBD was not strongly selective for the cancer cells based on metabolic activity alone. However, more substantial differences emerged when they examined CBD’s effects on specific proteins, apoptosis and cell-cycle progression.

CBD reduced FAM111B gene expression in both cell types, but significantly reduced FAM111B protein levels only in the fibrosarcoma cells. This suggests that CBD affected the production or stability of the protein differently in cancerous and noncancerous cells.

CBD also significantly reduced levels of BAG3 and Cyclin B1 in the fibrosarcoma cells. BAG3 helps cancer cells adapt to stress and resist death, while Cyclin B1 plays an important role in cell division.

The proportion of fibrosarcoma cells undergoing apoptosis increased from 3.55% in the untreated control group to 13.2% following CBD treatment. No statistically significant increase in apoptosis was observed among the noncancerous fibroblasts.

CBD also caused pronounced changes in the fibrosarcoma cells’ progression through the cell cycle. The percentage of cells in the Sub-G1 phase, which is associated with fragmented DNA and apoptosis, increased from 3.44% to 18.37%. The proportion in the G0/G1 phase increased from 28.30% to 39.17%.

At the same time, the proportion of fibrosarcoma cells in the DNA-replication S phase declined from 19.32% to 8.08%, while the proportion in the G2/M phase declined from 50.97% to 36.17%. Researchers said the pattern indicates that CBD impaired the cells’ ability to progress normally through the process of growth and division.

“These findings identify FAM111B- and BAG3-associated pathways as potential therapeutic vulnerabilities and support further investigation of CBD as a modulator of stress-adaptive and proliferative signaling in preclinical fibrosarcoma models,” the researchers concluded.

The study was conducted using a single cancer cell line in a two-dimensional laboratory setting, and the CBD concentrations were generally higher than levels typically found in human blood following standard clinical dosing. Researchers said the results should therefore be viewed as evidence of CBD’s molecular effects rather than proof that it can treat fibrosarcoma in patients.

Further studies using additional sarcoma cell lines, more clinically relevant CBD exposures and animal models will be needed to determine whether the findings could have therapeutic significance.