Jonathan Viehoever, Naveen Surya Velmani, Vignesh Basavaraj, Lahiru Gamage, Kai-Cheng Chan, Praveenkumar Basavaraj, Wen-Chin Huang,
Therapeutic interference of SREBP-mediated lipid metabolism by E-Xanthohumol attenuates prostate cancer progression.
https://doi.org/10.1016/j.bcp.2026.117859.
This preclinical study tested whether combining two plant-derived compounds—xanthohumol (from hops) and ursolic acid (found in foods such as apples, cranberries, and thyme)—could slow prostate-cancer development more effectively than either compound alone.
Researchers conducted experiments in six human and mouse prostate-cancer cell lines and in two mouse models:
- Mice implanted with HMVP2 prostate tumors.
- HiMyc mice genetically predisposed to develop prostate cancer.
The animals received standard food or food containing xanthohumol, ursolic acid, or both. Each compound constituted 0.2% of the supplemented diets. Synergy was assessed using the Bliss independence model.
The combination reduced cancer-cell survival and colony formation more strongly than either compound alone across all six tested cell lines. It also altered proteins governing cancer growth and cell-cycle progression: phosphorylated STAT3, cyclin D1, c-MYC, Cdc6, and phosphorylated Rb decreased, while the cell-cycle inhibitor p21 increased.
In the implanted-tumor model, the combined diet produced significantly smaller tumors than the control or either single-compound diet. The effect met the researchers’ criterion for synergy from day 21 onward. Tumors also showed:
- Reduced polyamine synthesis and lower levels of metabolites involved in that pathway.
- Changes consistent with suppression of epithelial-to-mesenchymal transition, a process associated with cancer invasion.
- Increased E-cadherin and decreased Twist1.
In HiMyc mice, the combination reduced progression from precancerous lesions to adenocarcinoma. This appeared to involve endoplasmic-reticulum stress, activation of the unfolded-protein response, and apoptosis. Neither compound alone produced comparable protection at the doses tested.
Body weight and food intake were not adversely affected, suggesting the mice tolerated the diets well.
The results support the biological plausibility of xanthohumol and ursolic acid acting together against prostate cancer through several mechanisms—disrupting growth signaling, slowing the cell cycle, changing tumor metabolism, suppressing invasive characteristics, and promoting cancer-cell death.
The limitation is that this was a laboratory and animal study, not a human clinical trial. Some experiments had small sample sizes—three replicates for several cell studies and approximately seven or eight mice per group in the implanted-tumor experiment—and some tissue analyses used pooled samples. The 0.2%-of-diet doses also cannot be translated directly into a safe or effective human supplement dose. Human absorption, metabolism, long-term safety, drug interactions, and clinical effectiveness remain unknown.
