Abstract
Apple is a rich source of bioactive phytochemicals that help improve health by preventing and/or curing many disease processes, including cancer. One of the apple polyphenols is phloretin [2′,4′,6′-Trihydroxy-3-(4-hydroxyphenyl)-propiophenone], which has been widely investigated for its antioxidant, anti-inflammatory and anti-cancer activities in a wide array of preclinical studies. The efficacy of phloretin in suppressing xenograft tumor growth in athymic nude mice implanted with a variety of human cancer cells, and the ability of the compound to interfere with cancer cells signaling, have made it a promising candidate for anti-cancer drug development. Mechanistically, phloretin has been reported to arrest the growth of tumor cells by blocking cyclins and cyclin-dependent kinases and induce apoptosis by activating mitochondria-mediated cell death. The blockade of the glycolytic pathway via downregulation of GLUT2 mRNA and proteins, and the inhibition of tumor cells migration, also corroborates the anti-cancer effects of phloretin. This review sheds light on the molecular targets of phloretin as a potential anti-cancer and anti-inflammatory natural agent.
Highlights
Cancer, a heterogenous disease process, still remains a major challenge for human health.Despite the development of a wide variety of anti-cancer therapies such as alkylating agents, various kinase inhibitors, hormone modulators, and very recently introduced immune checkpoint inhibitors, the incidence of and mortality from cancer is still increasing throughout the world
These biochemical processes include, but are not limited to, alterations in the activities of enzymes involved in carcinogen metabolism and detoxification, inappropriate amplification of intracellular signaling pathways regulating cell proliferation and apoptosis, tumor angiogenesis, invasion, metastasis, and dysregulation of host immune functions
Since exposure to ultra violet (UV) radiation is a major cause of skin cancer, this study suggests the potential of phloretin to inhibit UV-induced skin carcinogenesis
Summary
A heterogenous disease process, still remains a major challenge for human health. The course of neoplastic transformation of cells can be prevented by intervening with various biochemical processes that become abnormal as a result of DNA damage, and oxidative modifications of proteins and lipids upon exposure to potential carcinogens These biochemical processes include, but are not limited to, alterations in the activities of enzymes involved in carcinogen metabolism and detoxification, inappropriate amplification of intracellular signaling pathways regulating cell proliferation and apoptosis, tumor angiogenesis, invasion, metastasis, and dysregulation of host immune functions. Administration of phloretin significantly ameliorated trinitrobenzene sulfonic acid (TNBS)-induced colon inflammation and the loss of body weight in rats [24], suggesting the potential of this compound to prevent colorectal carcinogenesis This has been supported by a recent study demonstrating the effectiveness of phloretin in suppressing the growth of human colorectal cancer (COLO 205) tumor xenografts in Balb/c nude mice [25].
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