Role of capsaicin, circadian clock genes, and TRPV1 in colorectal carcinogenesis: Lessons and future directions

Disruptions in rhythm-regulating genes, termed circadian misalignment, have been increasingly associated with the progression of colorectal cancer (CRC), a significant global health challenge. Capsaicin (CAP), a bioactive compound found in chili pepper, has emerged as a promising modulator of clock genes, exhibiting anti-CRC potential. We propose a previously unrecognized dual-pathway mechanism where CAP may modulate circadian clock genes via both transient receptor potential vanilloid 1 (TRPV1)-dependent and TRPV1-independent pathways to inhibit colorectal carcinogenesis. Although the role of CAP in CRC prevention via clock gene regulation is compelling, direct mechanistic evidence remains limited. This paper also identifies several research gaps to underscore the necessity for further research to unlock its therapeutic potential and develop novel preventive strategies.