Comprehensive Review of Cancer Chemopreventive Agents Evaluated in Experimental Carcinogenesis Models and Clinical Trials

Abstract

Cancer chemoprevention refers to the use of pharmacological agents to inhibit, delay or reverse the multi-step process of carcinogenesis. The last two decades in particular have witnessed explosive growth in this emerging field of cancer chemoprevention. Extensive efforts to evaluate possible application of various chemopreventive agents, in individuals at high risk of neoplastic development have been carried out. Epidemiological studies suggest a protective role of several agents in reducing the risk of cancer. The protective action of all these agents is explained as a combination of various proposed mechanisms involving anti-oxidant, anti-inflammatory, immunomodulatory action, apoptosis induction, molecular association with carcinogen, cell cycle arrest, cell differentiation induction, antimicrobial effect, and anti- angiogenesis etc. Large numbers of candidate substances such as phytochemicals and their synthetic derivatives have been identified by a combination of in vitro and in vivo studies in a wide range of biological assays. However, a comprehensive description of these chemopreventive agents has not been extensively reviewed. In this review we discuss cancer chemopreventive agents in relation to their source, efficacy in cancer chemopreventive action in vivo and epidemiological data. The experimental carcinogenesis studies in different biological models, in addition to the contribution from our laboratory are summarized.

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

“…Chemoprevention has emerged as an ideal approach whereby the occurrence and progression of the disease can be prevented, slowed, or reversed by the administration of one or more naturally occurring and/or synthetic compounds [24][25][26] . Phytochemicals, including those obtained from fruits, vegetables, nuts and spices, have drawn a considerable amount of attention due to their ability to selectively kill tumor cells and suppress carcinogenesis in preclinical animal models [27][28][29][30][31][32][33] . A large number of these plant-derived substances have been shown to significantly prevent or delay cancer development in several high risk populations [34][35][36] .…”

Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells

“…The protective action of these agents is explained as a combination of various proposed mechanisms involving molecular association with carcinogens, the modulation of enzymes involved in biotransformation reactions (such as cytochrome p450 and glutathione S-transferase), anti-oxidant, anti-inflammatory, antiangiogenesis, and immunomodulatory actions, apoptosis induction, cell-cycle arrest, cell-differentiation induction, antimicrobial effects, tyrosine kinase inhibition, and others (Akiyama et al 1987;Chen et al 2003;Foti et al 2005;Moon et al 2006;Rufer and Kulling 2006;Chodon et al 2007;Choi and Kim 2008;Naithani et al 2008).…”

Metabolic regulation and redox activity as mechanisms for angioprevention by dietary phytochemicals

“…For a comprehensive treatise on the action of diet-derived chemopreventive agents, several excellent reviews have been recently published on this subject. 4,5 We have extensively studied the antiangiogenic and antimetastatic effects of different cancer chemopreventive compounds (collectively termed ''angiopreventive'' agents), including diet-derived phytochemicals such as EGCG, curcumin, hyperforin, xanthohumol, deguelin, CDDO triterpenoids and 4HPR. [6][7][8][9][10][11] In this review, we will focus on recent results on specific aspects of the biological activity of selected dietary phytochemicals relating to metabolic and redox regulation as a mechanism in ''angioprevention''.…”