Abstract

Norcantharidin (NCTD), a cantharidin derivative, induces ROS generation and is widely used to treat CRC. In this study, we clarified the role and mechanism of action of norcantharidin in increasing CRC sensitivity to radiotherapy. We treated the CRC cell lines LoVo and DLD-1 with NCTD (10 or 50 μmol/L), ionizing radiation (IR, 6 Gy), and a combination of the two and found that NCTD significantly inhibited the proliferation of CRC cells and enhanced their sensitivity to radiotherapy. NCTD induced ROS generation by decreasing the mitochondrial membrane potential, increasing mitochondrial membrane permeability, and promoting cytochrome C release from mitochondria into the cytoplasm. IR combined with NCTD induced ROS production, which activated the mitochondrial fission protein DRP1, leading to increased mitochondrial fission and CRC sensitivity to radiotherapy. NCTD also reduced CRC cell resistance to radiotherapy by blocking the cell cycle at the G2/M phase and decreasing p-CHK2, cyclin B1, and p-CDC2 expression. NCTD and IR also inhibited radiation resistance by causing DNA damage. Our findings provide evidence for the potential therapeutic use of NCTD and IR against CRC. Moreover, this study elucidates whether NCTD can overcome CRC radiation tolerance and provides insights into the underlying mechanisms.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.