Cancer Biology and Hormesis: Comments on Calabrese (2005)

Abstract

Large numbers of chemicals of a variety of types exhibit apparent hormetic effects on cultured human cancer cells, causing stimulation of cell growth or related changes at low doses, followed by inhibition at higher doses. Many of the studies listed are not fully convincing, due to lack of appropriate controls or sufficient number of doses. However, the proposed hormetic response seems firmly established in a subset of these experiments. Significance with regard to in vivo cancer growth has not been pursued and must be a priority for the future. For several examples where in vivo titers are known, such as, resveratrol, suramin, and tamoxifen, comparison of the dose and concentration ranges confirms that hormesis could be an issue in vivo. Further investigations are warranted, especially for therapeutic drugs, phytochemicals, and environmental toxicants.

Orally Bioavailable Metal Chelators and Radical Scavengers: Multifunctional Antioxidants for the Coadjutant Treatment of Neurodegenerative Diseases

“…10−13 Aβ also binds Zn to form neurotoxic plaque that results in localized oxidative stress and neuronal death. 14 Aβ plaque is also present in the retinas of patients with AMD 15,16 and in the lenses of AD patients with cataracts. 17 The increased presence of Aβ plaque in these agerelated diseases is accompanied by the dramatic loss of αB crystallin, 18 a zinc binding protein chaperone.…”

“…9 In AD, ROS is generated by mitochondrial dysfunction, the presence of β-amyloid peptide (Aβ) and redox metal ions such as Fe 2+ and Cu 2+ , and activated glial cells. 15 Increased Mn levels can also contribute to mitochondrial dysfunction as well as impaired energy metabolism, excitotoxic neuronal death, apoptotic death, and oxidation of cellular components. 10−13 Aβ also binds Zn to form neurotoxic plaque that results in localized oxidative stress and neuronal death.…”

“…An imbalance favoring oxidants can lead to protein, lipid-oxidation, and DNA tissue damage that is associated with age-related cataract, age-related macular degeneration (AMD), and Alzheimer’s disease (AD). − In addition to oxidative stress, an age-related accumulation of redox-active metals, such as iron and copper, also occurs in the lens, retina, and brain of patients with age related cataracts, AMD, and AD. − When combined with ROS, the increased presence of redox-active metal ions can promote further tissue damage by generating hydroxyl radicals through the Fenton reaction . In AD, ROS is generated by mitochondrial dysfunction, the presence of β-amyloid peptide (Aβ) and redox metal ions such as Fe 2+ and Cu 2+ , and activated glial cells . Increased Mn levels can also contribute to mitochondrial dysfunction as well as impaired energy metabolism, excitotoxic neuronal death, apoptotic death, and oxidation of cellular components. − Aβ also binds Zn to form neurotoxic plaque that results in localized oxidative stress and neuronal death .…”

“…Increased Mn levels can also contribute to mitochondrial dysfunction as well as impaired energy metabolism, excitotoxic neuronal death, apoptotic death, and oxidation of cellular components. − Aβ also binds Zn to form neurotoxic plaque that results in localized oxidative stress and neuronal death . Aβ plaque is also present in the retinas of patients with AMD , and in the lenses of AD patients with cataracts . The increased presence of Aβ plaque in these age-related diseases is accompanied by the dramatic loss of αB crystallin, a zinc binding protein chaperone.…”

Short communication. An in vitro approach for ecotoxicity testing of toxic and hazardous wastes

“…Hormesis represents a possible beneficial overcompensation in response to disruption in homeostasis to adverse stimulus. Hormesis effects have been observed from a broadly diversified spectrum of chemical classes (Anderson, 2005;Calabrese and Blain, 2005).…”