Usnic Acid and Its Evolving Role as a Potent Antineoplastic Agent.

Abstract

The recent article by Yokouchi et al. (2015) provided for highly interesting reading. Usnic acid (UNA) also exerts significant antineoplastic properties. UNA attenuates tumor growth in lung carcinomas. It mediates this role in part by enhancing Poly (ADP-ribose) polymerase [PARP] cleavage. As a result, UNA administration significantly accentuates intratumoral apoptosis. Singh et al. (2013) have recently demonstrated that UNA also upregulates p21/cip1 expression significantly. This results in accentuated intratumoral G0/G1 phase arrest. In addition, it downregulates cyclin D1 expression. These changes have recently been confirmed in A549 cell lines. At the same time, it induces mitochondrial membrane depolarization. Besides the above changes, UNA also has a negative impact on CDK4 and CDK6 expression thereby further mitigating tumor growth in pulmonary malignancies. Similarly, UNA reduces tumor growth in mammary malignancies. It primarily accentuates intratumoral apoptosis. In addition, Song et al. (2012) have recently demonstrated that UNA has an inhibitory effect on VEGFR2-mediated AKT and ERK1/2 signaling pathways. These changes have recently been confirmed in Bcap-37 cell lines. As a result, UNA has a negative impact on endothelial cell proliferation as well as migration. Tube formation is also attenuated concurrently thereby further limiting tumor growth in breast carcinomas. UNA plays a similar role in mitigating tumor growth in hepatocellular carcinomas. It mediates this role in part by attenuating CYP2E1 activity. In addition, UNA has a positive impact on UGT1A4 expression. Sahu et al. (2012) have recently demonstrated that at the same time, UNA accentuates cell cycle proteins cyclin C (CCNC) activity and attenuates Granulocyte-macrophage colony-stimulating factor (CSF2) activity. These changes have recently been confirmed in hepatoma cell lines (HepG2). UNA also mediates upregulation of Chemokine (C-C motif) ligand 21 [CCL21] activity and concurrent downregulation of cholesterol 7alpha-hydroxylase (CYP7A1) activity thereby further mitigating tumor growth in hepatocellular carcinomas. UNA also limits and restricts tumor growth in colorectal malignancies. UNA administration has a positive impact on reactive oxygen species (ROS) production. Backorova et al. (2012) have recently demonstrated that similarly UNA modulates Bax and Bcl-2 expression thereby inducing intratumoral apoptosis. In addition, it decreases the ‘‘mitochondrial membrane potential’’ significantly. These changes have recently been confirmed in HT-29 cell lines. Besides the above changes, UNA also accentuates caspase-3 activation thus further mitigating tumor growth in colon carcinomas. As is obvious from the above discussion, UNA possesses significant tumor growth limiting properties. It appears to be a promising antineoplastic agent, and further research is recommended to fully evaluate these effects of UNA.