Background: Usnic Acid (UA), also known as lichenol, has been reported to have inhibitory
effects on a variety of cancer cells, but its specific mechanism remained to be elucidated. Tumor
chemotherapy drugs, especially DNA damage chemotherapeutic drugs, target Chromosomal DNA, but
their spontaneous and acquired drug resistance are also an urgent problem to be solved. Therefore,
drug combination research has become the focus of researchers.
Methods: Here, we evaluated the tumor-suppressing molecular mechanism of UA in colorectal cancer
cells RKO from the perspective of the ATM-mediated DNA damage signaling pathway through H2O2
simulating DNA damage chemotherapeutic drugs. CCK8 cell proliferation assay was used to determine
the inhibition of RKO cells by hydrogen peroxide and UA alone or in combination, and wound
healing assay was applied to determine the effect of the drug on cell migration.
Results: Transfected cells with miRNA18a-5p mimics and inhibitors, MDC and DCFH-DA staining
for the measurement of autophagy and ROS, cell cycle and apoptosis were detected by flow cytometry,
expressions of microRNA and mRNA were determined by fluorescence quantitative PCR, and protein
by Western blot.
Discussion: We found that UA can upregulate ATM via miR-18a to activate the DNA damage signaling
pathway and inhibit the proliferation and migration of RKO cells in a concentration-dependent
Conclusion: At the same time, DNA damage responses, including cell cycle, autophagy, apoptosis and
ROS levels, are also regulated by UA. Therefore, UA combined with DNA damage chemotherapeutic
drugs may be an effective treatment for cancer.