Avenanthramide A

Avenanthramide A is an orally active phytoalexin that targets the RNA helicase DDX3 with a K_D of 8.8 μM. Avenanthramide A induces mitochondrial swelling and increased ROS production, and triggers apoptosis in CRC cells. Avenanthramide A inhibits smooth muscle cell proliferation and enhances nitric oxide production. Avenanthramide A can be used in research on colorectal cancer and atherosclerosis^[1][2]. In Vitro:Avenanthramide A binds most tightly to the ATP-binding domain-containing truncated DDX3^1-306 mutant (K_d = 7.11 μM), with weaker binding to the N-terminal DDX3^1-215 (K_d = 13.85 μM) and C-terminal DDX3^307-662 (K_d = 36.25 μM) mutants^[1].
Avenanthramide A (30 μM) potently inhibits the ATPase activity of purified recombinant human DDX3 protein^[1].
Avenanthramide A selectively reduces the viability of human DLD1 colorectal cancer cells while having minimal effect on normal human FHC colonic epithelial cells^[1].
Avenanthramide A (30 μM; 24 h) has reduced ability to suppress viability of human DLD1 colorectal cancer cells expressing DDX3^R287A or DDX3^R294A mutants, indicating these residues are critical for its anti-tumor activity^[1].
Avenanthramide A (30 μM) downregulates NDUFS2 and UQCRC1 expression in human DLD1 colorectal cancer cells expressing wild-type DDX3, DDX3^K255A, or DDX3^S290A, but not in cells expressing DDX3^R287A or DDX3^R294A[1].
Avenanthramide A (30 μM) induces ROS production in human DLD1 colorectal cancer cells expressing wild-type DDX3, DDX3^K255A, or DDX3^S290A, but not in cells expressing DDX3^R287A or DDX3^R294A[1]. In Vivo:Avenanthramide A (30 mg/kg; p.o.; daily; 21 days) significantly suppresses DLD1 xenograft tumor growth in BALB/c nude mice, reduces tumor proliferation and DDX3 expression, induces tumor cell apoptosis, and exhibits no detectable systemic toxicity^[1].