Anacardic acid, from cashew nut shell liquid, is a Histone acetyltransferase (HAT) inhibitor with IC50 values of 8.5µM and 5µM for p300 and p300/CBP-associated factor (PCAF), respectively[1]. Anacardic acid efficiently inhibits Tip60, the MYST family of HATs, with an IC50 value of 9µM[2]. Anacardic acid stimulation of neutrophil extracellular traps occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors[3]. Anacardic acid inhibits both inducible and constitutive NF-κB activation, suppresses the activation of IκBα kinase that leads to abrogation of phosphorylation and degradation of IκBα, and inhibits acetylation and nuclear translocation of p65[4]. Anacardic acid has been widely used in tumor research to inhibit tumor blood vessels and the growth of various cancer cells[5].
In vitro, Anacardic acid treatment for 48 hours significantly inhibited the viability of GH3 and MMQ cells, with IC50 values of 52µM and 37.9µM, respectively[6]. Incubating A549 cells with 3µg/ml Anacardic acid for 24 hours induced endoplasmic reticulum stress and autophagy, and inhibited the expression of p-PERK and the downstream substrate p-eIF2α[7]. Treatment with 100µM Anacardic acid for 24 hours inhibited the proliferation of MDA-MB-231 cells, induced cell cycle arrest at the G0/G1 phase, inhibited cell invasion and migration, and induced cell apoptosis[8].
In vivo, Anacardic acid treatment via intraperitoneal injection at a dose of 2mg/kg/day for 14 days inhibited tumor growth in HepG2 xenograft tumor mice, without affecting body weight[9]. A single intraperitoneal injection of Anacardic acid (25mg/kg) mitigated the edema induced by carrageenan in mice 1 hour later and reduced the licking behavior and abdominal writhing response[10].
References:[1] Balasubramanyam K, Swaminathan V, Ranganathan A, et al. Small molecule modulators of histone acetyltransferase p300[J]. Journal of Biological Chemistry, 2003, 278(21): 19134-19140.
[2] Hamad F B, Mubofu E B. Potential biological applications of bio-based anacardic acids and their derivatives[J]. International Journal of Molecular Sciences, 2015, 16(4): 8569-8590.
[3] Hollands A, Corriden R, Gysler G, et al. Natural product anacardic acid from cashew nut shells stimulates neutrophil extracellular trap production and bactericidal activity[J]. Journal of Biological Chemistry, 2016, 291(27): 13964-13973.
[4] Sung B, Pandey M K, Ahn K S, et al. Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-κB–regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-κBα kinase, leading to potentiation of apoptosis[J]. Blood, The Journal of the American Society of Hematology, 2008, 111(10): 4880-4891.
[5] Wu Y, He L, Zhang L, et al. Anacardic acid (6-pentadecylsalicylic acid) inhibits tumor angiogenesis by targeting Src/FAK/Rho GTPases signaling pathway[J]. The Journal of pharmacology and experimental therapeutics, 2011, 339(2): 403-411.
[6] Sukumari-Ramesh S, Singh N, Jensen M A, et al. Anacardic acid induces caspase-independent apoptosis and radiosensitizes pituitary adenoma cells[J]. Journal of neurosurgery, 2011, 114(6): 1681-1690.
[7] Seong Y A, Shin P G, Yoon J S, et al. Induction of the endoplasmic reticulum stress and autophagy in human lung carcinoma A549 cells by anacardic acid[J]. Cell biochemistry and biophysics, 2014, 68(2): 369-377.
[8] Zhao Q, Zhang X, Cai H, et al. Anticancer effects of plant derived Anacardic acid on human breast cancer MDA-MB-231 cells[J]. American journal of translational research, 2018, 10(8): 2424.
[9] Huang H, Hua X, Liu N, et al. Anacardic acid induces cell apoptosis associated with induction of ATF4-dependent endoplasmic reticulum stress[J]. Toxicology letters, 2014, 228(3): 170-178.
[10] Gomes Junior A L, Islam M T, Nicolau L A D, et al. Anti-inflammatory, antinociceptive, and antioxidant properties of anacardic acid in experimental models[J]. ACS omega, 2020, 5(31): 19506-19515.