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Page 2 of 36 Dave et al. J Cancer Metastasis Treat 2020;6:46 I http://dx.doi.org/10.20517/2394-4722.2020.106

Keywords: Chemoprevention, phytochemicals, resveratrol, curcumin, anthocyanins, silibinin, lycopene,
epigallocatechin-3-gallate, anti-cancer activity

INTRODUCTION
Overall, cancer is the second leading cause of death in the US and a major public health issue throughout
[1]
the world. Approximately 1,762,450 new cancer cases are estimated in the US in 2019 , and 18.1 million
[2]
new cases worldwide. In 2018, 9.6 million deaths were attributed to this disease . Given these astounding
demographics, and the associated pain, suffering and economic burden, the scientific and medical
community continuously strive for better treatment options, improved palliative care, and effective
preventative strategies. In this context, the role of diet in cancer has attracted considerable attention. This
is especially compelling given that epidemiological studies have demonstrated regular consumption of
phytochemicals from dietary sources like fruits, vegetables, herbs, and teas is associated with reduced risk
[3,4]
of chronic diseases including cancer, cardiovascular disease and inflammatory disorders .

Cancer chemoprevention can be classified into primary, secondary, and tertiary measures. Populations
with no overt cancer risk factors, or those ostensibly at high risk due to factors such as successful surgical
resection or family history, can be grouped under primary measures. Patients with pre-malignant lesions
bearing risk of progressing to an invasive cancer (e.g., ductal carcinoma in situ) can be grouped under
secondary measures. In these cases, standard protocols of chemopreventive practice would be highly
[5]
desirable, but scarcely come into play . People in primary and secondary chemoprevention categories
may be advised or decide on their own to increase dietary phytochemical consumption or to use over
the counter products such as non-steroidal anti-inflammatory drugs. Finally, tertiary measures can be
[6]
considered for patients with cancer relapses . A unique example of a tertiary chemopreventive measure
is the administration of tamoxifen (or structural relatives), or aromatase inhibitors, for patients diagnosed
[7]
with breast cancer .

Around two and half thousand years ago, Hippocrates advised “let food be thy medicine and medicine be
thy food”. This remains a powerful statement, as graphically illustrated in Figure 1. An inverse relationship
between adequate fruit and vegetable consumption and cancer incidence has been established. In fact, it has
been suggested that cancer incidence could be reduced by over 50% if people consume at least five servings
[9]
of fruits and vegetables per day . On the other hand, obesity is generally associated with poor health and
chronic illness, and there are certain foods that can act as carcinogens and initiate tumor formation.

Secondary metabolites (phytochemicals) are typically generated in plants to afford protection against
external threats such as UV, fungal infection, and the generation of free radicals. The compounds so
produced show a remarkable array of structural diversity. Notably, ingestion of these phytochemicals
[10]
provide human beings with protective effects as well , perhaps by reducing oxidative stress (ROS) and
inflammation [3,11] . However, the mechanisms by which phytochemicals function in a chemopreventive
capacity are certainly intricate and multifaceted, as described to some extent in this review.

Interestingly, cancer and aging share several hallmarks in terms of the genetic pathways and biochemical
processes. For example, DNA repair mechanisms are affected by ROS and this may result in the
deregulation of signaling pathways such as p53 and nuclear factor-κB (NF-κB). In turn, such deregulation
[12]
may accelerate aging and cancer development . In principal, antioxidants sourced from phytochemicals
[13]
may neutralize ROS and attenuate oxidative stress . Further, as deregulation of signaling pathways is
involved in progression of inflammatory diseases, modulation of these processes by phytochemicals may
[14]
down-regulate proinflammatory factors . Considering the general safety of dietary phytochemicals,