Exploring the Potential of Capsaicin in Cancer Therapy: In Vitro and In Vivo Effects and Their Mechanism of Action

Cancer is the second most major cause of human mortality globally, and according to the International Agency for Research on Cancer (IARC), more than 19 million cancer cases are prevalent worldwide and approximately 10 million cases of death are reported in 2020. Cancer prevention and treatment is very challenging due to the involvement of multiple systems, genetic factors and pathways which manifest over a long period. The ineffectiveness and side effects of modern cancer treatment have motivated researchers to explore phytochemicals for alternative or supportive cancer therapy. The phytochemical capsaicin is a well-known naturally occurring plant secondary metabolite, which is responsible for imparting pungency or hotness in chilli peppers of the Capsicum genus. The medicinal properties of capsaicin have been explored by researchers since its discovery in the nineteenth century to the modern day. The discovery of the capsaicin receptor, transient receptor potential subfamily V type 1 (TRPV1), has shed light on the mechanisms by which capsaicin induces some of its pharmacological effects if not all. Capsaicin has been explored as an anti-cancer agent and has shown wide applications against various types of cancer because of its availability, affordability, non-toxicity and fewer side effects. This chapter highlights the in vitro and in vivo effects of capsaicin in different types of cancers, namely breast, lung, colorectal, prostate, gastric, liver, pancreatic, bladder, skin, bone, and leukemia, and helps to understand the mechanism of action of capsaicin, which elucidates the potential of capsaicin as an anti-cancer agent. Capsaicin has been reported to display a chemopreventive role by regulating the crucial stages of carcinogenesis, i.e., initiation, promotion and malignancy (metastasis). The mechanism of action of capsaicin involves inhibition of cell viability, cell cycle arrest at different phases, induction of angiogenesis, and apoptosis, via modulation of the levels of various downstream intermediaries. Newer approaches using nanotechnology are explored to improve the bioavailability of capsaicin, and synthetic non-pungent analogues are also developed to overcome the shortcomings of capsaicin. Co-treatment of capsaicin along with chemotherapy or radiation therapy are also explored. Further studies involving robust models and cancer patients may help in better understanding and utilisation of this compound.