Anti-cancer efficacy and mechanisms of usnic acid

Cancer is the second deadly disease after cardiovascular diseases. The presently available therapeutic strategies of cancer are insufficient for the cure and betterment of cancer patients. Herein, we have reviewed the therapeutic potential of a lichenic secondary metabolite, the usnic acid, with special emphasis on its anti-cancer efficacy and associated mechanisms. Usnic acid has various biological activities that have been explored and it is utilized by humans from ancient times throughout the globe. A summary of the anti-cancer properties of usnic acid in different cancer types and models is presented. Usnic acid has shown to inhibit the cancer cell proliferation by suppressing the clonogenic potential, decreasing the expression of PCNA (proliferating cell nuclear antigen), and activating the tumor suppressor genes. Primarily, usnic acid induces reactive oxygen species (ROS) in cancer cells that lead to DNA damage, further causing the activation of DNA damage response that finally initiates the apoptotic pathways. The ROS induction was found to activate the JNK pathway. It also depolarizes the mitochondrial membrane, induces the release of cytochrome-c, and activates the caspase cascade and cleavage of PARP that ultimately results in programmed cell death of cancer cells. Overall, this lichen metabolite has a strong efficacy against cancer cells, which warrants further investigation for its potential clinical uses.