Abstract
The use of the anthelmintic drug pyrvinium pamoate (PP) in cancer therapy has been extensively investigated in the last decade. PP has been shown to have an inhibitory effect in colorectal cancer (CRC), but the underlying mechanism remains elusive. We aimed to investigate the antitumor activity and mechanisms of PP in CRC. In the present study, we used CCK-8 assays, colony formation assays, and western blotting to reveal that PP effectively suppressed CRC cell proliferation and the AKT-dependent signaling pathway in a concentration-dependent and time-dependent manner. Flow cytometric analysis and fluorescence microscopy demonstrated that PP increased intracellular reactive oxygen species (ROS) accumulation. We found that the inhibitory effect of PP on cell proliferation and AKT protein expression induced by PP could be partially reversed by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, the results also demonstrated that PP inhibited cell migration by modulating epithelial-to-mesenchymal transition (EMT)-related proteins, including E-cadherin and vimentin. In conclusion, our data suggested that PP effectively inhibited cell proliferation through the ROS-mediated AKT-dependent signaling pathway in CRC, further providing evidence for the use of PP as an antitumor agent.
Highlights
Colorectal cancer (CRC) is the third most common cancer among males and the second most common cancer among females [1]
CRC still ranks as the third most fatal cancer globally, and a large proportion of patients have a poor quality of life due to multiple dysfunctions caused by treatments [1, 3]
We demonstrated the antiproliferative effect of pyrvinium pamoate (PP) and illustrated its potential mechanisms of action on human CRC cell lines
Summary
Colorectal cancer (CRC) is the third most common cancer among males (after lung and prostate cancers) and the second most common cancer among females (after breast cancer) [1]. CRC still ranks as the third most fatal cancer globally, and a large proportion of patients have a poor quality of life due to multiple dysfunctions caused by treatments [1, 3]. Different levels of ROS exhibit dual effects on cells [8,9,10]. Cell repair dysfunction and increased oxidative stress contribute to irreversible damage [10]. Compared with their normal counterparts, tumor cells have higher ROS levels [9]. Cancer treatments targeting ROS may result in fewer side effects for patients [11]. Previous studies have shown that some agents can induce cell cycle arrest and apoptosis by regulating the level of ROS.
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