Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Abstract

To cite this version:Breeze E. Cavell, Sharifah S. Syed Alwi, Alison Donlevy, Graham Packham. Anti-angiogenic effects of dietary isothiocyanates; mechanisms of action and implications for human health. Biochemical Pharmacology, Elsevier, 2010, 81 (3) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Isothiocyanates and angiogenesis -3 - AbstractIsothiocyanates (ITCs) are electrophilic compounds derived from plants and are thought to play a major role in the potential chemopreventive effects associated with high intake of cruciferous vegetables. ITCs are also being evaluated for chemotherapeutic activity in early phase clinical trials. In addition to their effects on carcinogen metabolism and cancer cell survival and proliferation, ITCs have been shown to effectively interfere with angiogenesis in vitro and in vivo. Angiogenesis is the development of a new blood supply from existing vasculature and is required for tumours to develop beyond a small size limit determined by the diffusion limit for oxygen. Inhibition of angiogenesis may play a key role in the potential chemopreventive/chemotherapeutic activity of ITCs. In this review we highlight recent data demonstrating that ITCs have anti-angiogenic activity and identify potential molecular targets for these effects, including hypoxia-inducible factor (HIF), nuclear factor B (NF-B), activator protein 1 (AP1) and tubulin. We also discuss these findings in light of the potential chemopreventive/chemotherapeutic effects of ITCs.

Phytochemicals of papaya and its traditional health and culinary uses – A review

“…It is rich in benzyl isothiocyanate (BITC) which may provide potential for use in chemoprevention of cancer. It has been suggested that the anti-carcinogenic effects of isothiocyanates are related to their capacity to induce phase II enzymes such as glutathione S-transferase, nicotinamide adenine dinucleotide phosphate and quinine reductase (Cavell et al, 2011;Nakamura et al, 2000). The glucosinolates are known to be degraded into isothiocyanates by enzymatic action of plantspecific myrosinase or intestinal microbiota in the human body (Basu and Haldar, 2008).…”

Differential induction of apoptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent

“…PEITC has received considerable attention due to its potential chemopreventive and chemotherapeutic activities (Cavell et al 2011;Cheung and Kong 2010;Hayes et al 2008). PEITC decreases carcinogen-induced cancer development in vivo and interferes with the activation of carcinogens via inhibition of phase I metabolism and activation of phase II metabolism.…”

Synergistic effects of phenylhexyl isothiocyanate and LY294002 on the PI3K/Akt signaling pathway in HL-60 cells

“…PHI (LKT Laboratories, Inc., St. Paul, MN, USA), >98% pure, was dissolved in 75% methanol to a stock concentration of 5 mmol/l and stored at -20˚C following positive pressure filtration through a 0. 22 Cell culture. The human AML cell line HL-60 was obtained from the China Center for Type Culture Collection (Beijing, China).…”

“…Isothiocyanates are best known for their antioxidative, anticancer chemotherapeutic, chemopreventive, and anti-angiogenic properties (21,22). PHI, a synthetic isothiocyanate, is able to induce cell growth arrest and apoptosis in a number of types of tumor cell by inhibiting histone deacetylation, histone methylation and DNA methylation, and by remodeling chromatins (23)(24)(25)(26)(27).…”