PubMed: Cannabidiolic acid activates the expression of the PPARβ/δ target genes in MDA-MB-231 cells

PubMed: Cannabidiolic acid activates the expression of the PPARβ/δ target genes in MDA-MB-231 cells

Arch Biochem Biophys. 2022 Oct 10:109428. doi: 10.1016/j.abb.2022.109428. Online ahead of print.

ABSTRACT

Cannabidiolic acid (CBDA) can activate peroxisome proliferator-activated receptor-α (PPARα) and PPARγ. Whether CBDA can activate PPARβ/δ has not been examined sufficiently to date. Since previous studies showed that triple-negative breast cancer cells respond to activation of PPARβ/δ, the present study examined the effect of CBDA in MDA-MB-231 cells and compared the activities of CBDA with known PPARβ/δ agonists/antagonists. Expression of the PPARβ/δ target genes angiopoietin-like 4 (ANGPTL4) and adipocyte differentiation-related protein (ADRP) was increased by CBDA. Interestingly, ligand activation of PPARβ/δ with GW501516 caused an increase in expression of both ANGPTL4 and ADRP, but the magnitude of this effect was markedly increased when co-treated with CBDA. Specificity of these effects were confirmed by showing that CBDA-induced expression of ANGPTL4 and ADRP is mitigated in the presence of either a PPARβ/δ antagonist or an inverse agonist. Results from these studies suggest that CBDA can synergize with PPARβ/δ and might interact with endogenous agonists that modulate PPARβ/δ function.

PMID:36228705 | DOI:10.1016/j.abb.2022.109428

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