Cinobufagin suppresses colorectal cancer growth via STAT3 pathway inhibition

Colorectal cancer (CRC) has become one of the most common types of cancer with the highest morbidity and mortality rates globally. Cinobufagin, a natural product extracted from toad venom and a major active ingredient in cinobufotalin, exhibits high antitumor activity. Here, we investigated the in vitro and in vivo antitumor activities of cinobufagin and explored the underlying mechanisms in CRC. Cinobufagin could inhibit proliferation, migration, invasion and promote apoptosis of HCT116, RKO, and SW480 cells in vitro. Mechanistically, cinobufagin simultaneously suppressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and blocked the interleukin-6 (IL6)-induced nuclear translocation of STAT3. IL6 activated the STAT3 pathway, subsequently inducing epithelial-mesenchymal transition (EMT). Furthermore, cinobufagin suppressed EMT in CRC by inhibiting the STAT3 pathway. Animal experiments clearly showed that cinobufagin could reduce tumor growth. Cinobufagin may be used clinically as a novel STAT3 inhibitor for CRC adjuvant therapy.

Automated summary

Cinobufagin, a natural product extracted from toad venom, exhibits high antitumor activity by inhibiting proliferation, migration, invasion, and promoting apoptosis of colorectal cancer cells in vitro and in vivo. The underlying mechanism involves suppression of the STAT3 pathway, leading to inhibition of epithelial-mesenchymal transition.