Cancer Prevention with Promising Natural Products: Mechanisms of Action and Molecular Targets

Abstract

Cancer is the second leading cause of death worldwide. There is greater need for more effective and less toxic therapeutic and preventive strategies. Natural products are becoming an important research area for novel and bioactive molecules for drug discovery. Phytochemicals and dietary compounds have been used for the treatment of cancer throughout history due to their safety, low toxicity, and general availability. Many active phytochemicals are in human clinical trials. Studies have indicated that daily consumption of dietary phytochemicals have cancer protective effects against carcinogens. They can inhibit, delay, or reverse carcinogenesis by inducing detoxifying and antioxidant enzymes systems, regulating inflammatory and proliferative signaling pathways, and inducing cell cycle arrest and apoptosis. Epidemiological studies have also revealed that high dietary intakes of fruits and vegetables reduce the risk of cancer. This review discusses potential natural cancer preventive compounds, their molecular targets, and their mechanisms of actions.

Grandisin induces apoptosis in leukemic K562 cells

“…Thus, significant effort has been invested in finding new phytochemicals with antitumoral properties. Throughout history, natural compounds have been used for the treatment of cancer due to their safety, low toxicity, and availability from natural sources (Pratheeshkumar et al, 2012). Grandisin is a lignan extracted from Piper solmsianum which presents antitumoral properties as well as antimalarial and trypanocidal activities (Martins et al, 2003;Bernardes et al, 2006;Valadares et al, 2011).…”

Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective PPAR-α-Dependent Inhibition of Akt/mTOR Pathway

“…Cancer prevention by natural products has become an integral part of cancer control, and plant-derived molecules have been thus regarded as potential novel leads for developing antiangiogenic drugs (Kuttan et al, 2011;Pratheeshkumar et al, 2012). Palmitoylethanolamide (PEA) is an endogenous N-acylethanolamide, acting as an 'on demand' autacoid local antiinflammatory amide (ALIA)-mide involved in many pathophysiological processes ranging from pain control, neuroprotection and antiinflammatory response (Calignano et al, 2001;Lambert et al, 2001;Levi-Montalcini et al, 1996;LoVerme et al, 2005a).…”

Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway

“…Among the various signaling molecules involved in the angiogenic process, vascular endothelial growth factor (VEGF) and nitric oxide (NO) are thought to be the key signaling molecules responsible for neo-vascularization (4)(5)(6). Once hypersecreted, VEGF binds to its type 2 receptor (VEGFR-2) and mediates the regulation of different pathways in the target cells, mainly the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway (7,8) and the phosphop38 mitogen activated protein kinase (MAPK)-dependent activation of nuclear factor κB (NF-κB) (9,10). Activation of the NF-κB and Akt/mTOR pathways increases the levels of the inducible nitric oxide synthase (iNOS) isoform, leading to the release and accumulation of nitric oxide (NO) that acts as a pro-angiogenic stimulus on the blood vessels and favors neo-vascularization in solid tumors (5,11).…”