Fibrosarcoma, a rare and aggressive cancer arising from fibrous connective tissues. It presents a significant therapeutic challenge. A recent study on the overexpression of the human FAM111B gene in fibrosarcoma compared normal epithelial tissues, suggesting it may represent a viable therapeutic target. It is common knowledge that many studies have reported on the anti-cancer properties of Cannabidiol (CBD). However, the molecular mechanisms or targets by with it elicits this property is not fully understood. Consequently, this study investigated the potential of Cannabidiol (CBD) to downregulate FAM111B expression and its implications for apoptosis and cell cycle regulation in fibrosarcoma cells (HT1080) compared to non-cancerous cells (FG0). Utilizing quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, we established the IC50 values for CBD in HT1080 and FG0 cells. These findings indicate that CBD affects both cell lines with comparable selectivity, suggesting its potential as an adjuvant in cancer therapy.

CBD treatment led to a notable downregulation of FAM111B at both mRNA and protein levels across both cell lines. In HT1080 cells, CBD significantly modulated key regulators of the cell cycle and apoptosis, including Cyclin B1, p21, and BAG3. The upregulation of p21, coupled with the downregulation of Cyclin B1 and BAG3, resulted in an increased arrest of cells in the G0 phase and elevated apoptosis rates. Importantly, CBD did not alter the expression of FAM111A, a closely related gene. Our findings suggest that CBD effectively targets FAM111B, influencing critical cellular pathways associated with cell cycle and apoptosis in fibrosarcoma. This research demonstrates the potential therapeutic utility of CBD in the treatment of fibrosarcoma while also demonstrating its impact on non-cancerous cells. Further investigation will be essential to fully understand the underlying mechanisms and to assess CBD's potential as an adjunct in cancer therapy.

Learning Objectives:

• Summarize the established anti-cancer properties of Cannabidiol (CBD) while identifying the existing gaps in understanding its molecular mechanisms of action

• Explore the justification for researching CBD's influence on FAM111B expression and its potential implications for cancer therapy.