Redox-sensitive mechanisms of phytochemical-mediated inhibition of cancer cell proliferation (Review)

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)

George Loo, Professor (Creator)

Institution

The University of North Carolina at Greensboro (UNCG )

Web Site: http://library.uncg.edu/

Abstract: Phytochemicals are potential cancer chemopreventive agents, based partly on cellular research establishing that phytochemicals inhibit the proliferation of cancer cells. To elucidate the mechanism of phytochemicals, a basic understanding is needed of what stimulates cancer cell proliferation. Cancer cells, particularly those that are highly invasive or metastatic, may require a certain level of oxidative stress to maintain a balance between undergoing either proliferation or apoptosis. They constitutively generate large but tolerable amounts of H₂O₂ that apparently function as signaling molecules in the mitogen-activated protein kinase pathway to constantly activate redox-sensitive transcription factors and responsive genes that are involved in the survival of cancer cells as well as their proliferation. With such a reliance of cancer cells on H₂O₂, it follows that if the excess H₂O₂ can be scavenged by phenolic phytochemicals having antioxidant activity, the oxidative stress-responsive genes can be suppressed and consequently cancer cell proliferation inhibited. On the other hand, phenolic phytochemicals and another group of phytochemicals known as isothiocyanates can induce the formation of H₂O₂ to achieve an intolerable level of high oxidative stress in cancer cells. As an early response, the stress genes are activated. However, when the critical threshold for cancer cells to cope with the induced oxidative stress has been reached, key cellular components such as DNA are damaged irreparably. In conjunction, genes involved in initiating cell cycle arrest and/or apoptosis are activated. Therefore, phytochemicals can either scavenge the constitutive H₂O₂ or paradoxically generate additional amounts of H₂O₂ to inhibit the proliferation of cancer cells.

Redox-sensitive mechanisms of phytochemical-mediated inhibition of cancer cell proliferation (Review)
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Additional Information

Publication

Journal of Nutritional Biochemistry 14, 64-73.

Language: English

Date: 2003

Keywords

Hydrogen peroxide, Isothiocyanates, Phenolic phytochemicals, Signal transduction, Redox-sensitive genes

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