Food-based natural products for cancer management: Is the whole greater than the sum of the parts?

Abstract

The rise in cancer incidence and mortality in developing countries together with the human and financial cost of current cancer therapy mandates a closer look at alternative ways to overcome this burgeoning global healthcare problem. Epidemiological evidence for the association between cancer and diet and the long latency of most cancer progression have led to active exploration of whole and isolated natural chemicals from different naturally occurring substances in various preclinical and clinical settings. In general the lack of systemic toxicities of most ‘whole’ and ‘isolated’ natural compounds, their potential to reduce toxic doses and potential to delay the development of drug-resistance makes them promising candidates for cancer management. This review article examines the suggested molecular mechanisms affected by these substances focusing to a large extent on prostate cancer and deliberates on the disparate results obtained from cell culture, preclinical and clinical studies in an effort to highlight the use of whole extracts and isolated constituents for intervention. As such these studies underscore the importance of factors such as treatment duration, bioavailability, route of administration, selection criteria, standardized formulation and clinical end points in clinical trial design with both entities. Overall lack of parallel comparison studies between the whole natural products and their isolated compounds limits decisive conclusions regarding the superior utility of one over the other. We suggest the critical need for rigorous comparative research to identify which one of the two or both entities from nature would be best qualified to take on the mantle of cancer management.

Introduction

The global map of cancer prevalence is rapidly changing. While the western world is witnessing a decrease in most cancer-related mortality, incidence and mortality continue to rise rapidly in developing and underdeveloped countries. The International Agency for Research on Cancer reported that 64.9% of cancer-deaths in 2012 occurred in less developed regions of the world [1]. About 97% of growth in world population in 2012 was also attributed to that of developing nations. Considering this unexpected growth, and higher life expectancies, it is projected that new cancer cases will dramatically increase from 14.1 million in 2012–19.3 million by 2025 [1], [2]. This crippling global cancer scenario raises immense concerns regarding accessibility to treatment due to excessive cost of modern cancer care in general and limited access to exorbitant therapeutics in developing countries in particular. Further, increased survival is also accompanied by increased healthcare costs to monitor many recurrent cancers. These devastating facts underscore the need for economical and novel interventions that may have a larger global reach. The ability to use naturally occurring materials to manage cancer is an appealing alternative to overcome these alarming statistics. Given the large numbers of starting materials in nature, the various isolated compounds, complexities of different cancers and the recapitulation of preclinical tumor models make it very clear that we have to ensure that the most commonly tested natural whole extract and/or their isolated compounds are fully and scientifically vetted to facilitate their use for cancer management. Chemoprevention in general and prevention with phytochemicals has been widely studied in 4 of the most common cancers including lung, colon, breast and prostate. In this review we focus largely on prostate cancer. Cell culture studies that reveal mechanistic aspects of the effects of these compounds and their parent extracts are also presented. As discussed here validation of these molecular mechanisms may facilitate their use as surrogate markers of efficacy in clinical trials.