CHEMOPREVENTIVES: UNTAPPED GENII THAT COMPROMISE THE SCIENCE OF THE “KILLERS”

by Professor E.O. Farombi, Department of Biochemistry

ABSTRACT

Exposure of humans to disruptive chemicals in air, water and diet has been shown to be related to various life-threatening diseases including cancer as well as reproductive health problems such as decreased fertility, and impaired spermatogenesis. It has been identified that dietary exposure to aflatoxins in grains and peanuts, nitrosamines in meat and drinks, polycyclic aromatic hydrocarbons in charcoal grilled meat and agricultural pesticides in aquatic species through food chain contributes largely to the development of these diseases. Providentially, certain protective compounds are inherently contained in the human diet. Thus, convincing and compelling evidence arising from both pre-clinical and clinical investigations indicate that plant-based diets rich in a wide variety of phytochemicals with potent antioxidant properties are effective in preventing or reversing chronic degenerative diseases. Antioxidants are considered to bring about their effects by attenuating oxidative events that contribute to the pathophysiology of these diseases. For instance, there is now good evidence linking high intake of phytochemicals, with antioxidant properties, in fresh fruits and vegetables, with low incidence of certain cancer. In this connection, the lecturer whose main research thrust over the past 23 years is chemoprevention explained the term as the use of agents (especially naturally occurring) to inhibit, mitigate, delay, reverse or retard multistage process of chronic diseases including cancer.

In this lecture, the role of Free radicals and Reactive Oxygen Species (ROS) generation in the pathology of environmental compounds such as Atrazine, Bonny light crude oil, Municipal landfill leachates as well as some Antimalarial drugs especially when taken at overdose was discussed. Interference with drug biotransformation enzymes and their ability to induce cellular oxidative stress was also described. Using the“comet assay” (Single cell gel electrophoresis technique) and bone marrow micronuclei induction,the inaugural lecturer and his colleagues established the potential genotoxic effects of some of these environmental compounds.

Deploying several biochemical techniques and panel of assays involving ROS, the lecturer and co-workers characterised the antioxidant properties of several plant-based phytochemicals and extracts such as a- and b-carotenes from red pam oil, kolaviron from Garcinia kola and polyphenolic compounds from soybeans. The lecturer, his doctoral student and their collaborators isolated and characterized for the first time a sesquiterpene lactone named Epivernodalol from Vernonia amygdalina effective against HT-144 (skin melanoma) cell line and its relevance in treating skin cancer amongst other biological values was discussed.

The lecturer highlighted and discussed the chemopreventive properties of selected phytochemicals- Curcumin from Turmeric, 6-Gingerol from Ginger, Soy polyphenols from Soybeans, Epivernodalol and phenolics from Vernonia amygdalina and Kolaviron from Garcinia kola seed. Oxidative stress and inflammation have been identified as ‘co-conspirators’ in the development of certain degenerative diseases including cancer. The series of experimental and mechanistic findings discussed in this lecture showed that these phytochemicals elicited striking antioxidant and anti-inflammatory activities as basic mechanisms of chemoprevention against these diseases. Specifically, Kolaviron compromised oxygen-derived radical-induced DNA damage, decreased LDL oxidation in relation to the development of atherosclerosis and cardiac dysfunction, compromised stress response and inflammatory proteins, down regulated inflammation-associated redox-regulated transcription factors and abrogated apoptosis and related caspases. The recent advances in neuroprotective mechanisms of Kolaviron was also highlighted thus opening up a new therapeutic window in progressive neurodegenerative diseases such as Parkinson’s disease.

The ability of these antioxidant and anti-inflammatory phytochemicals to exert chemopreventive effects by modulating intracellular signaling cascades, in vivo redox status and pro-inflammatory mediators qualify them as new therapeutic signatures for chemoprevention of inflammation and free radical-associated diseases.