Cinobufagin: Unveiling the hidden bufadienolide's promise in combating alimentary canal cancer development and progression - a comprehensive review.

Cinobufagin (CB) is a bufadienolide extracted from the parotid gland of frogs. This compound is a Na + /K + -ATPase inhibitor and has shown promise in oncological research since its anti-cancer properties have been the subject of essential studies, including induction of apoptosis, cell cycle arrest, and preventing cancer cell proliferation and migration. Besides, CB also has anti-inflammatory properties, which are necessary for chemoprevention and cancer targeting. Due to the novelty of this issue and considering that no previous review has addressed CB's promise against alimentary canal cancers yet, the present review brings together evidence from pre-clinical cellular studies that relate to the effects of CB on digestive tract cancers, emphasizing aspects such as molecular signaling pathways, mechanisms of action, effectiveness of the compound, and possible clinical outcomes. The gathered evidence demonstrated that this compound decreased cell viability and, consequently, increased the induction of apoptosis, acting on the cell cycle and inhibiting cell proliferation, directly affecting the migration and invasion of digestive tract tumors in the models tested. The molecular pathways involved are JAK/STAT3, Akt, Bcl-2, caspases, and NF-κB. Our review demonstrates the significant potential of CB against digestive tract cancers, highlighting the compound's therapeutic potential against alimentary canal cancers, including inducting apoptosis, inhibiting tumor growth, and modulating cancer signaling pathways. However, some issues limit the power of CB, such as the limited concentration ranges and unknown interactions with the tumor microenvironment, which demonstrates the need for long-term safe studies and the lack of human validation. Future endeavors combining CB with radiotherapy and chemotherapies would also enhance our understanding of using CB as synergistic therapy against alimentary tract cancers. Therefore, our review recommends future clinical trials to provide more significant evidence of human efficacy and safety, advocating for green healthcare principles and enhanced patient care quality.