Mimosine: A multifaceted non-protein amino acid with potent anticancer potential across diverse malignancies

Mimosine, a non-protein amino acid found in Mimosa pudica and Leucaena species, exhibits potent anticancer properties across various malignancies, including glioma, breast, melanoma, cervical, hepatocellular, prostate, pancreatic, osteosarcoma, leukemia, lymphoma, and lung cancers. Structurally similar to tyrosine, mimosine inhibits tyrosinase and acts as an iron chelator, disrupting critical cellular processes such as DNA synthesis and cell cycle progression. Its primary mechanism involves inducing apoptosis via the intrinsic mitochondrial pathway, driven by reactive oxygen species (ROS) generation, which activates caspase-9 and caspase-3, leading to programmed cell death. Mimosine also induces G0/G1 phase cell cycle arrest by upregulating cyclin-dependent kinase inhibitors (p21, p27) and downregulating cyclins (D1, A, E) and CDKs, mediated through HIF-1α stabilization and Myc suppression. Its iron-chelating activity inhibits ribonucleotide reductase, stalling DNA replication and causing double-strand breaks. Additionally, mimosine modulates signaling pathways, including MAPK (p38, JNK) and NF-κB, and regulates tumor suppressor genes like NDRG1 and Btg2, enhancing its anti-proliferative and anti-metastatic effects. In specific cancers, such as breast (MCF-7) and cervical (HeLa), mimosine exhibits context-dependent effects, including estrogenic activity or selective translation regulation. Despite challenges in cell permeability, advances in peptide synthesis and click chemistry offer promise for enhancing mimosine’s therapeutic potential. Its multifaceted mechanisms, including ROS-mediated apoptosis, cell cycle arrest, and enzyme inhibition, position mimosine as a promising candidate for developing novel anticancer therapies.