Circaea mollis Siebold & Zucc. Induces Apoptosis in Colorectal Cancer Cells by Inhibiting c-Myc Through the Mediation of RPL5

Colorectal cancer remains a significant global health concern. In this study, we investigated the anticancer potential of Circaea mollis Siebold & Zucc. (CS&Z), a traditional medicinal plant known for its anti-inflammatory, anti-arthritic, and antioxidant properties, in the treatment of colorectal cancer. We found that CS&Z induces apoptosis and G1/S phase cell cycle arrest in colorectal cancer cells, primarily through the suppression of the proto-oncogene c-Myc. Specifically, the depletion of RPL5, a ribosomal protein associated with c-Myc regulation, reversed the suppression of c-Myc by CS&Z. Additionally, when co-administered with the standard chemotherapeutic agents doxorubicin and 5-fluorouracil, CS&Z demonstrated synergistic effects, thereby further emphasizing its potential efficacy as a therapeutic option for the treatment of colorectal cancer. Moreover, the constituents of CS&Z, detected through liquid chromatography–mass spectrometry analysis, reportedly exhibit anticancer activities. Taken together, our findings suggest that CS&Z holds promise as a natural product capable of modulating oncogenic signaling in colorectal cancer and may serve as a complementary agent in future therapeutic strategies.