Sodium selenite-induced oxidative stress and apoptosis in human hepatoma HepG2 cells

Abstract

The mechanisms involved in the anti‐carcinogenic activity of selenium remain to be elucidated. In the present study, we examined sodium selenite‐induced oxidative stress and apoptosis in a human hepatoma cell line (HepG2). Sodium selenite (10 μM) exerted clear cytotoxic effect, as shown by the significant increase of lactate dehydrogenase leakage. Selenite‐induced DNA alterations in apoptosis were studied by: 1. comet assay; 2. TdT‐mediated dUTP nick end‐labeling assay. In addition, characteristic apoptotic morphological alterations were also observed in selenite‐treated cells. Our results clearly show that Se‐induced cell death occurs predominantly in the form of apoptosis. Selenite‐induced oxidative stress was evaluated by the measurement of reactive oxygen species production using lucigenin‐dependent chemiluminescence. The involvement of glutathione in selenite‐induced oxidative stress was further demonstrated by the concurrent decline of intracellular reduced glutathione and increase of oxidized glutathione contents in Se‐treated cells. Moreover, the finding that selenite‐induced oxidative stress and apoptosis was significantly attenuated by superoxide dismutase, catalase and deferoxamine provides additional evidence to suggest that Se‐induced oxidative stress mediates the induction of apoptosis, a mechanism related to the anti‐carcinogenic and chemopreventive effect of Se. Int. J. Cancer 81:820–828, 1999. © 1999 Wiley‐Liss, Inc.

Selenium, Apoptosis, and Colorectal Adenomas

“…Our results concerning the relation between selenium and apoptosis in humans were contrary to results from several laboratory studies, suggesting that selenium increased anticancer apoptotic activity (34)(35)(36)(37)(38)(39)(40)(41)(42). There are several reasons that our results may differ from laboratory studies.…”

“…The possibility that selenium may increase anticancer apoptotic activity has been suggested by several carcinogenesis studies (34)(35)(36)(37)(38)(39)(40)(41)(42). It is unclear how selenium might induce apoptosis; however, several selenium metabolites, such as hydrogen selenide, methylselenol, and selenodiglutathione, are being researched (43)(44)(45).…”

Selenium has a protective role in caspase-3-dependent apoptosis induced by H2O2 in primary cultured pig thyrocytes

“…It has been suggested that selenium cytotoxicity is related to the generation of free radicals that induces apoptosis (33). However, the selenite concentrations (10 -100 nmol/l) used here to experimentally modulate the GPx activity were within physiological range, and no unwanted side effects of the selenium substitution were observed.…”

Bimodal actions of selenium essential for antioxidant and toxic pro-oxidant activities: The selenium paradox (Review)

“…The superoxide anion (O 2 •-) is produced intracellularly by transferring electrons leaked from the electron transport chain in mitochondria and from NADPH cytochrome P450 reductase in the endoplasmic reticulum to oxygen, as well as by the action of several enzymes including NADPH oxidase, lipooxygenase, cyclooxygenase, flavoenzymes (e.g., xanthine oxidase), and uncoupled nitric oxide synthase (47). In particular, the superoxide anion is also formed endogenously by the reaction of selenium compounds such as selenite, selenium dioxide, diselenides, and selenocysteine, and with thiols such as reduced GSH or L-cysteine (3,11,48). The generation of superoxide anions by selenium has been confirmed by treating cells with exogenous GSH or selenite; this has also been observed by adding isolated mitochondria to selenium-containing compounds, including selenite, selenocysteine, selenocystamine, and selenodioxide, to GSH, or to both (10,49,50).…”