Unraveling TRPV1's Role in Cancer: Expression, Modulation, and Therapeutic Opportunities with Capsaicin

Abstract

Cancer is a global health challenge with rising incidence and mortality rates, posing significant concerns. The World Health Organization reports cancer as a leading cause of death worldwide, contributing to nearly one in six deaths. Cancer pathogenesis involves disruptions in cellular signaling pathways, resulting in uncontrolled cell growth and metastasis. Among emerging players in cancer biology, Transient Receptor Potential (TRP) channels, notably TRPV1, have garnered attention due to their altered expression in cancer cells and roles in tumorigenesis and progression. TRPV1, also known as the capsaicin receptor, is pivotal in cancer cell death and pain mediation, offering promise as a therapeutic target. Activation of TRPV1 triggers calcium influx and affects cell signaling linked to growth and death. Additionally, TRPV1 is implicated in cancer-induced pain and chemo-sensitivity, with upregulation observed in sensory neurons innervating oral cancers. Also, when capsaicin, a compound from chili peppers, interacts with TRPV1, it elicits a "hot" sensation and influences cancer processes through calcium influx. Understanding TRPV1's multifaceted roles in cancer may lead to novel therapeutic strategies for managing cancer-related symptoms and improving patient outcomes. The current review elucidates the comprehensive role of capsaicin in cancer therapy, particularly through the TRPV1 channel, highlighting its effects in various cells via different signaling pathways and discussing its limitations.

Keywords: TRPV1; cancer pain; cancer therapy; capsaicin; signaling pathways.

Figure 1

TRPV1 channel in cancer dynamics: This figure illustrates the role of the TRPV1 channel in cancer progression/inhibition and highlights the effects of capsaicin on various cancer cells. Key signaling pathways affected by capsaicin, such as the PI3K/Akt and MAPK pathways, are depicted, showcasing the molecular mechanisms involved in cancer cell modulation (illustration created using BioRender). Arrow up means upregulation, down means down regulation.

Figure 2

Molecular mechanism of apoptosis mediated by capsaicin-activated TRPV1 in various cancer cells. (Illustration created using Biorender.).