Abstract

Despite the extensive knowledge on cancer nature acquired over the last years, the high incidence of this disease evidences a need for new approaches that complement the clinical intervention of tumors. Interestingly, many types of cancer are closely related to dietary habits associated with the Western lifestyle, such as low fruit and vegetable intake. Recent advances around the old-conceived term of chemoprevention highlight the important role of phytochemicals as good candidates for the prevention or treatment of cancer. The potential to inhibit angiogenesis exhibited by many natural compounds constituent of plant foods makes them especially interesting for their use as chemopreventive agents. Here, we review the antitumoral potential, with a focus on the antiangiogenic effects, of phenolic and polyphenolic compounds, such as quercetin or myricetin; terpenoids, such as ursolic acid or kahweol; and anthraquinones from Aloe vera, in different in vitro and in vivo assays, and the available clinical data. Although clinical trials have failed to assess the preventive role of many of these compounds, encouraging preclinical data support the efficacy of phytochemicals constituent of diet in the prevention and treatment of cancer, but a deeper understanding of their mechanisms of action and better designed clinical trials are urgently needed.

Concluding Remarks and Future Challenges

The use of nontoxic plant-derived natural compounds as chemopreventive agents in cancer has become an attractive approach in the last years, since it represents a low-cost, easily accessible, and broad-spectrum alternative to conventional drugs. Additionally, the high number of bioactive compounds contained in plant foods that display antitumor and antiangiogenic effects in experimental models should prompt us to undoubtedly assess the feasibility of their use in cancer prevention.

While broad experimental evidence obtained for these compounds clearly points to their capability to target events involved in cancer initiation and progress, their application to cancer prevention is still far away from being clinically established. For many of these compounds, clinical trials are still very limited, contradictory, inconclusive, or even inexistent, making it extremely difficult to clarify the level of efficacy of these compounds in cancer prevention, if any, as well as their preventive role on the population and the suitable regimens needed to achieve the desired health benefits. In this context, a significant effort is needed to improve the design of clinical trials, paying special attention to the target population, as well as to the pharmacokinetics and pharmacodynamics of the compounds. In terms of cancer treatment, however, the use of these compounds in combination with typical therapeutic agents comes as a rather interesting approach, as it would allow the reduction in the aggressiveness and side effects caused by these drugs, while also improving their effects.

Undoubtedly, a deeper understanding of the mechanism of action of the compounds in the context of the hallmarks of cancer is necessary, mainly attending to the pleiotropic character of their reported biological actions. In line with this, it is worth encouraging basic, translational, and clinical research to better integrate the available information to improve the outcome of clinical trials, and eventually determine the health benefits and efficacy of plant-derived bioactive compounds in the chemoprevention of cancer.