Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

Amin, A.R.M. R. et al. (2015) Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds. Seminars in Cancer Biology, 35, S55-S77. (doi:10.1016/j.semcancer.2015.02.005) (PMID:25749195)

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Abstract

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bilsland, Dr Alan and Keith, Professor Nicol
Authors: Amin, A.R.M. R., Karpowicz, P. A., Carey, T. E., Arbiser, J., Nahta, R., Chen, Z. G., Dong, J.-T., Kucuk, O., Khan, G. N., Huang, G. S., Mi, S., Lee, H.-Y., Reichrath, J., Honoki, K., Georgakilas, A. G., Amedei, A., Amin, A., Helferich, B., Boosani, C. S., Ciriolo, M. R., Chen, S., Mohammed, S. I., Azmi, A. S., Keith, W. N., Bhakta, D., Halicka, D., Niccolai, E., Fujii, H., Aquilano, K., Ashraf, S. S., Nowsheen, S., Yang, X., Bilsland, A., and Shin, D. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Seminars in Cancer Biology
Publisher:Elsevier
ISSN:1044-579X
ISSN (Online):1096-3650
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Seminars in Cancer Biology 35:S55-S77
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
580721Optimisation of telomerase expression repressorsNicol KeithCancer Research UK (CAN-RES-UK)C301/A14762ICS - EXPERIMENTAL THERAPEUTICS
580722Optimisation of telomerase expression repressorsNicol KeithCancer Research UK (CAN-RES-UK)C301/A14762ICS - EXPERIMENTAL THERAPEUTICS