Oxidative Stress and Tumour Cell Proliferation

Abstract

The effects of oxidant stress were studied in immortalised hamster (BHK-21) and rat (208F) cell lines before and after transformation to the malignant state with polyoma virus, or activated H-ras, respectively. Whilst intracellular superoxide production was detectable in both transformed and immortalised cells the rate was somewhat higher in the transformed cells which have lower levels of superoxide dismutase. Because growth of transformed cells was particularly depressed in the presence of MTT, a tetrazolium compound reduced by superoxide, the possible role of active oxygen species in the promotion of cell growth was examined. Low levels of hydrogen peroxide were stimulatory towards both immortalised and transformed cells. In the case of H-ras transformed rat cells, paraquat was also stimulatory provided serum was present in the growth medium. In the absence of serum, paraquat was notably inhibitory but inhibition could be alleviated by addition of low concentrations of alpha-tocopherol (10(-8)M) to the serum-depleted medium. Although depletion of serum from the growth medium also leads to lower cell proliferation, subsequent experiments showed that alpha-tocopherol addition to serum-free medium was sufficient to restimulate growth. In the case of transformed cells, yields of cells were even greater than that encountered in the presence of 10% serum. Thus whilst certain active oxygen species (e.g. hydrogen peroxide) may have a role in promoting the growth of transformed and immortalised cells the necessity for antioxidant protection is important.

A redox cycle within the cell cycle: ring in the old with the new

“…Additionally, we found the fluorescence of a pro-oxidant sensitive dye was maximal in late S and G 2 þ M phases of the HeLa cell cycle compared to G 1 (Goswami et al, 2000). Additional reports from other laboratories have shown sub-lethal doses of ROS (O 2 À and H 2 O 2 ) added exogenously stimulated proliferation in cultured hamster fibroblasts (Burdon et al, , 1990Stirpe et al, 1991;Burdon and Gill, 1993). Interestingly, the effect of metabolic redox reactions on growth was not exclusive to mammalian cells, but can also be seen in Dictyostelium discoideum, one of the simplest organisms capable of forming multicellular structures.…”

Resveratrol Inhibits Drug-Induced Apoptosis in Human Leukemia Cells by Creating an Intracellular Milieu Nonpermissive for Death Execution

“…Whereas an overwhelming accumulation of intracellular reactive oxygen species could create an oxidatively stressed environment leading to necrosis, a slight increase is a stimulus for cellular proliferation (13,14). Pro-oxidant intracellular milieu is a hallmark of many tumor cells and is believed to endow tumor cells with a survival advantage over their normal counterparts (15,16).…”

Role of the plasma membrane ROS-generating NADPH oxidase in CD34+ progenitor cells preservation by hypoxia

“…As the specific second messengers in signaling cascades, ROS were documented to stimulate proliferation in a variety of mammalian cell types (Rao and Berk, 1992;Wartenberg et al, 1999;Burdon et al, 1990). This work detected that CD34 + cells were stimulated by cytokine combinations associated with the generation of ROS.…”