**Background**
The G protein-coupled receptor 84 (GPR84) is a receptor primarily expressed in immune cells and is activated by medium-chain fatty acids. Activation of GPR84 plays a critical role in modulating inflammatory responses and the production of pro-inflammatory cytokines, such as interleukin-12 (IL-12). In the context of oncology, the modulation of the immune microenvironment is a key strategy for enhancing the efficacy of cancer therapies. Recent studies have highlighted the potential of GPR84 activation to trigger potent anti-tumor immune responses, making it an attractive target for treating various malignancies. Therefore, in this context, we will introduce a potent GPR84 activator – 3-Hydroxydodecanoic acid.
**Definition**
3-Hydroxydodecanoic acid is a medium-chain fatty acid and human endogenous metabolite that acts as an agonist of GPR84, exhibiting an EC50 value of 1.31 μM for the inhibition of forskolin-stimulated cAMP accumulation in CHO cells.
**In Vitro and In Vivo Studies**
According to the 3-Hydroxydodecanoic acid description, this compound serves as a powerful tool for studying immune-mediated tumor suppression. In vitro, 3-Hydroxydodecanoic acid (1-100 μM; 1 h) has been shown to induce lipid peroxidation in the rat cerebral cortex, resulting in increased TBA-RS levels. Furthermore, agonist activity was confirmed in CHO cell membranes co-expressing human GPR84 and beta-arrestin2, with an EC50 of 1.31 μM for cAMP inhibition and 3.25 μM for beta-arrestin 2 recruitment.
Regarding 3-Hydroxydodecanoic acid in vivo activity, the compound demonstrates significant anti-tumor effects in C57BL/6JRj mice bearing MC38 tumors. When administered via intraperitoneal injection (i.p.) on days 6, 9, and 12, it significantly reduced tumor growth. This effect was dependent on GPR84 receptor signaling and was characterized by increased IL-12 production and higher infiltration of CD8+ T cells within the tumors. Additionally, 3-Hydroxydodecanoic acid showed a strong synergistic anti-tumor effect when combined with 5-FU. These findings suggest that 3-Hydroxydodecanoic acid cancer research applications could extend to colon cancer, lung cancer, and melanoma. In conclusion, 3-Hydroxydodecanoic acid is a GPR84 agonist that promotes anti-tumor immunity via IL-12 production and T cell infiltration.
Keywords
3-Hydroxydodecanoic acid, 1883-13-2, Endogenous Metabolite, colon cancer, lung cancer, and melanoma, anticancer, mice., Inhibitor, inhibitor, inhibit
References
[1] Tonin AM, et al. Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain. Neurochem Int. 2010 Jul;56(8):930-6.
[2] Katkeviciute E, et al. Bacteria-derived 3-hydroxydodecanoic acid induces a potent anti-tumor immune response via the GPR84 receptor. Cell Rep. 2025 Feb 26;44(3):115357.