Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is best known as the compound that gives chili peppers their sought-after spicy sensation. However, capsaicin may do much more than that. Research has linked it to anticarcinogenic benefits—although that’s been disputed by some. Here’s a look at how it is thought to function.
In order to metastasize, cancer cells must travel from the primary tumor site to other places within the body, most often via the surrounding stroma (i.e., connective tissue), blood vessels, and lymph nodes. The ability of the cells to travel to distant sites is known as cell migration, while the ability of the cells to degrade membrane proteins and enter the target tissue is known as cell invasion.
The epithelial-mesenchymal transition (EMT) is one process that neoplastic cells use in order to migrate. EMT allows polarized epithelial cells that are normally bound to a tissue’s basement membrane to undergo a series of molecular changes to become mobile mesenchymal cells. Capsaicin has been found to suppress several EMT transcription factors, thereby stalling the process (Friedman et al. 2019). Other studies have looked at capsaicin in combination with various chemotherapeutic agents meant to suppress EMT and have found that it enhances the effects of such drugs (Friedman et al. 2019).
A 2014 in vitro study found that capsaicin inhibited bile duct cancer cell migration and invasion in a dose-dependent manner, with up to 90% less cell invasion seen in the capsaicin-treated group than in the control group (Wutka et al. 2014). Further studies produced similar results, with suppressed migration and invasion seen in melanoma, fibrosarcoma, bladder cancer, and stomach cancer (Zhang et al. 2020).
Angiogenesis is the process by which new blood vessels are formed from the existing vasculature, enabling the body to deliver oxygen and nutrients to various tissues. However, it is also critical for tumor growth and progression, as tumor cells too require blood vessels to obtain oxygen and nutrients (Friedman et al. 2019). Capsaicin has demonstrated antiangiogenesis activity in non-small-cell lung carcinoma by downregulating vascular endothelial growth factor (VEGF) (Chakraborty et al. 2014). It was shown to have a similar effect on myeloma but appeared to increase levels of VEGF in human melanoma, highlighting the need for further research (Friedman et al. 2019).
The perceived spiciness of capsaicin is related to its interaction with the transient receptor potential vanilloid (TRPV) family of ion channel receptors. In sensory neuron fibers, the activation of the TRPV receptors by capsaicin leads to an increased influx of calcium ions, which depolarizes the neuron and causes the burning sensation associated with spiciness (Cunha et al. 2021). While the mechanism is not fully understood, researchers believe that the same influx of calcium ions may trigger apoptosis (cell death) in cancer cells. Tumor cells treated with capsaicin have their mitochondrial membranes disrupted, generally precipitating apoptosis (Cunha et al. 2021).
Capsaicin can induce apoptosis by other means as well. In hepatocellular and pancreatic carcinomas, for example, capsaicin-induced apoptosis occurs via activation of caspase-3, a protease that catalyzes the cleavage of critical cellular proteins (Wutka et al. 2014). Capsaicin has demonstrated apoptotic effects in a wide variety of cancers (Zhang et al. 2020).
Most studies investigating capsaicin’s effects on cancer were done in vivo in animals, usually mice, or in vitro. In both instances, capsaicin was administered directly to the subjects. While the doses administered were generally in the range of daily intake, it is unclear if the same effects would be seen with normal dietary intake of capsaicin from food, which varies greatly among individuals (Popescu et al. 2021). Moreover, most in vitro studies prolonged cell exposure to capsaicin in order to observe cell proliferation. Capsaicin is quickly absorbed and metabolized, though, so again, it is unclear if the same effects would be seen in human studies (Popescu et al. 2021). More research is needed before capsaicin can be recommended as an anticarcinogenic agent.