Corosolic acid (CA) is a plant-derived terpenoid compound with many health benefits. However, the anti-tumor effects of CA in bladder cancer remain unexplored. Here, we found that CA inhibited bladder tumor both in vitro and in vivo, and had no significant toxicity in mice. With the aid of transcriptomics and proteomics, we elucidated the regulatory network mechanism of CA inhibiting bladder cancer. Through cell viability detection, cell fluorescence staining and flow cytometry, we discovered that CA inhibited bladder cancer mainly through blocking cell cycle. Interestingly, CA played anticancer roles by distinct mechanisms at different concentrations: low concentrations (<7.0 μg/ml) of CA mainly inhibited DNA synthesis by downregulating TOP2A and LIG1, and diminished mitosis by downregulating CCNA2, CCNB1, CDC20, and RRM2; high concentrations (≥7.0 μg/ml) of CA induced cell death through triggering mitophagy via upregulating NBR1, TAXBP1, SQSTM1/P62, and UBB. CA, as a natural molecule of homology of medicine and food, is of great significance for the prevention and treatment of cancer patients following clarifying its anti-cancer mechanism. This study provides a comprehensive understanding of the pharmacological mechanism of CA inhibition in bladder cancer, which is helpful for the development of new anti-tumor drugs based on CA.
Keywords: Bladder cancer; Cell cycle; Corosolic acid; DNA replication; Mitophagy.
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