Cannabidiol selectively downregulates FAM111B expression and induces apoptosis in fibrosarcoma cells: an in vitro study.
5 affiliations
- 1Hair and Skin Research Laboratory, Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
- 2Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa.
- 3Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
- 4Hair and Skin Research Laboratory, Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa. [email protected].
- 5Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa. [email protected].
Abstract
Background
Fibrosarcoma is a rare and aggressive soft tissue sarcoma with limited therapeutic options and poor outcomes in advanced disease. Family with sequence similarity 111 member B (FAM111B) has emerged as a pro-tumorigenic factor associated with dysregulated cell survival and proliferation. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, exhibits anticancer activity in multiple malignancies, but its effects on FAM111B expression and downstream pathways in fibrosarcoma remain unclear.Methods
The effects of CBD were evaluated in human fibrosarcoma (HT1080) cells and non-cancerous human fibroblasts (FG0). Cell metabolic activity was assessed using an MTT assay. Gene and protein expression were determined by real-time quantitative PCR and Western blotting, respectively. Apoptosis and cell-cycle distribution were assessed by flow cytometry using Annexin V-FITC/propidium iodide (PI) and PI staining alone, respectively. Statistical analyses were performed using an unpaired Student's t-test or a two-way analysis of variance (ANOVA) followed by Šídák's post hoc multiple comparisons test, as appropriate.Results
CBD reduced metabolic activity in both HT1080 and FG0 cells in a dose-dependent manner, with comparable IC₅₀ values (28.95 ± 3.15 µM and 30.75 ± 9.12 µM, respectively), indicating limited selectivity based on metabolic activity alone. CBD significantly reduced FAM111B mRNA expression by approximately 3-fold in HT1080 cells and 2-fold in FG0 cells; however, a significant reduction in FAM111B protein expression was observed only in HT1080 cells, CBD treatment was associated with marked downregulation of BAG3 and Cyclin B1 proteins, increased apoptosis (Annexin V-positive cells: 3.55 ± 0.78% vs. 13.20 ± 4.56%), and altered cell-cycle progression characterized by increased Sub-G1 (3.44 ± 1.10% vs. 18.37 ± 0.83%) and G0/G1 (28.30 ± 1.57% vs. 39.17 ± 0.85%) populations, with corresponding reductions in the S- and G2/M-phase populations. These effects were markedly attenuated in non-cancerous fibroblasts.Conclusions
CBD exerts context-dependent anticancer effects in HT1080 fibrosarcoma cells by selectively suppressing FAM111B protein expression, promoting apoptosis, and disrupting cell-cycle progression. 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.
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BibTeX
@article{naicker2026cannabidiol,
title = {{Cannabidiol selectively downregulates FAM111B expression and induces apoptosis in fibrosarcoma cells: an in vitro study.}},
author = {Danielle Naicker and Falone Sunda and Cenza Rhoda and Hygon Mutavhatsindi and Nonhlanhla Khumalo and Afolake Arowolo},
journal = {Journal of cannabis research},
year = {2026},
month = aug,
doi = {10.1186/s42238-026-00481-1},
url = {https://europepmc.org/article/MED/42958469},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cannabidiol selectively downregulates FAM111B expression and induces apoptosis in fibrosarcoma cells: an in vitro study.
AU - Danielle Naicker
AU - Falone Sunda
AU - Cenza Rhoda
AU - Hygon Mutavhatsindi
AU - Nonhlanhla Khumalo
AU - Afolake Arowolo
PY - 2026
DA - 2026/08/01
JO - Journal of cannabis research
DO - 10.1186/s42238-026-00481-1
UR - https://europepmc.org/article/MED/42958469
AB - Background Fibrosarcoma is a rare and aggressive soft tissue sarcoma with limited therapeutic options and poor outcomes in advanced disease. Family with sequence similarity 111 member B (FAM111B) has emerged as a pro-tumorigenic factor associated with dysregulated cell survival and proliferation. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, exhibits anticancer activity in multiple malignancies, but its effects on FAM111B expression and downstream pathways in fibrosarcoma remain unclear.Methods The effects of CBD were evaluated in human fibrosarcoma (HT1080) cells and non-cancerous human fibroblasts (FG0). Cell metabolic activity was assessed using an MTT assay. Gene and protein expression were determined by real-time quantitative PCR and Western blotting, respectively. Apoptosis and cell-cycle distribution were assessed by flow cytometry using Annexin V-FITC/propidium iodide (PI) and PI staining alone, respectively. Statistical analyses were performed using an unpaired Student's t-test or a two-way analysis of variance (ANOVA) followed by Šídák's post hoc multiple comparisons test, as appropriate.Results CBD reduced metabolic activity in both HT1080 and FG0 cells in a dose-dependent manner, with comparable IC₅₀ values (28.95 ± 3.15 µM and 30.75 ± 9.12 µM, respectively), indicating limited selectivity based on metabolic activity alone. CBD significantly reduced FAM111B mRNA expression by approximately 3-fold in HT1080 cells and 2-fold in FG0 cells; however, a significant reduction in FAM111B protein expression was observed only in HT1080 cells, CBD treatment was associated with marked downregulation of BAG3 and Cyclin B1 proteins, increased apoptosis (Annexin V-positive cells: 3.55 ± 0.78% vs. 13.20 ± 4.56%), and altered cell-cycle progression characterized by increased Sub-G1 (3.44 ± 1.10% vs. 18.37 ± 0.83%) and G0/G1 (28.30 ± 1.57% vs. 39.17 ± 0.85%) populations, with corresponding reductions in the S- and G2/M-phase populations. These effects were markedly attenuated in non-cancerous fibroblasts.Conclusions CBD exerts context-dependent anticancer effects in HT1080 fibrosarcoma cells by selectively suppressing FAM111B protein expression, promoting apoptosis, and disrupting cell-cycle progression. 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.
SN - 2522-5782
ER -