β-carotene at high concentrations induces apoptosis by enhancing oxy-radical production in human adenocarcinoma cells

Palozza, Paola; Calviello, Gabriella; Serini, Simona; Maggiano, Nicola; Lanza, Paola; Ranelletti, Franco O.; Bartoli, Gianna Maria

doi:10.1016/s0891-5849(01)00488-9

Cited by 113 publications

(61 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We reported pro-apoptotic effects of canthaxanthin in both human colon adenocarcinoma and melanoma cells (33). In addition, our recent observation shows that -carotene was able to induce apoptosis in human colon adenocarcinoma cells (34) as well as in human leukemia cells (27 ), although such effects were evidenced at different concentrations of the carotenoid in the two cell types. Our experiments regarding the proapoptotic effects of the carotenoid highlight several points: a) undifferentiated cells were more susceptible to¯-carotene than differentiated ones; b)¯-carotene deeply decreased the expression of Bcl-2, a protooncogene product involved in protecting cells from apoptosis; c) apoptosis was induced through a p53-independent mechanism; d) the proapoptotic effect was strictly related to changes in intracellular redox potential.…”

Section: Effects On Cell Proliferation Differentiation and Apoptosismentioning

confidence: 91%

Mitogenic and Apoptotic Signaling by Carotenoids: Involvement of a Redox Mechanism

Palozza

Serini²,

Nicuolo³

et al. 2001

IUBMB Life

Self Cite

View full text Add to dashboard Cite

SummaryThe potential for carotenoids to modulate tumor growth is currently under investigation. Although epidemiological studies evidence that a high intake of vegetables, rich in carotenoids, decreases cancer incidence and mortality, clinical trials demonstrate that supplementation of¯-carotene to chronic smokers or to asbestos workers increases the risk for lung cancer. These contradictory ndings have renewed interest in elucidating the mechanism of action of carotenoids in biological systems. In this review, we show evidence for mitogenic and apoptotic effects of carotenoids and we support the hypothesis that these molecules may act as anticarcinogens or as procarcinogens through a redox mechanism. In particular, we report demonstrations for the anti-oxidant or pro-oxidant effects of carotenoids in vitro and in vivo, focusing our attention on the relationship existing between cell growth and redox status.

show abstract

Section: Effects On Cell Proliferation Differentiation and Apoptosismentioning

confidence: 91%

Mitogenic and Apoptotic Signaling by Carotenoids: Involvement of a Redox Mechanism

Palozza

Serini²,

Nicuolo³

et al. 2001

IUBMB Life

Self Cite

View full text Add to dashboard Cite

show abstract

“…Palozza and colleagues showed a proapoptotic effect of β-carotene in different cancer cell lines (including human colon and leukemic cancer cell lines), but the cell lines had varying degree of sensitivity to β-carotene (143,145,146). The same group investigated the role of β-carotene in attenuation of apoptosis via regulation of NF-κB in colon and leukemic cancer cell lines (148).…”

Section: Dietary Nutrients and Influence On Cancer Cells Carotenoidsmentioning

confidence: 99%

Redox Regulation by Intrinsic Species and Extrinsic Nutrients in Normal and Cancer Cells

McEligot

Yang²,

Meyskens³

2005

Annu. Rev. Nutr.

125

View full text Add to dashboard Cite

■ Abstract Cells in multicellular organisms are exposed to both endogenous oxidative stresses generated metabolically and to oxidative stresses that originate from neighboring cells and from other tissues. To protect themselves from oxidative stress, cells are equipped with reducing buffer systems (glutathione/GSH and thioredoxin/thioredoxin reductase) and have developed several enzymatic mechanisms against oxidants that include catalase, superoxide dismutase, and glutathione peroxidase. Other major extrinsic defenses (from the diet) include ascorbic acid, β-carotene and other carotenoids, and selenium. Recent evidence indicates that in addition to their antioxidant function, several of these redox species and systems are involved in regulation of biological processes, including cellular signaling, transcription factor activity, and apoptosis in normal and cancer cells. The survival and overall well-being of the cell is dependent upon the balance between the activity and the intracellular levels of these antioxidants as well as their interaction with various regulatory factors, including Ref-1, nuclear factor-κB, and activating protein-1.

show abstract

“…It has been reported to induce apoptosis in cancer cells, including leukemia, adenocarcinoma, and melanoma cells (Palozza et al 2001(Palozza et al , 2003a. Studies demonstrated that the anticancer effect of b-carotene derives from its pro-oxidant activity (Palozza et al 2002;Guruvayoorappan and Kuttan 2007), anti-oxidant action (Mishra et al 2013), regulation of cell differentiation (Lim et al 2014), or cell cycle arrest (Gloria et al 2014).…”

Section: Introductionmentioning

confidence: 99%

β-Carotene-induced apoptosis is mediated with loss of Ku proteins in gastric cancer AGS cells

et al. 2015

View full text Add to dashboard Cite

High dietary intakes and high blood levels of bcarotene are associated with a decreased incidence of various cancers. The anticancer effect of b-carotene is related to its pro-oxidant activity. DNA repair Ku proteins, as a heterodimer of Ku70 and Ku80, play a crucial role in DNA double-strand break repair. Reductions in Ku70/80 contribute to apoptosis. Previously, we showed that reactive oxygen species (ROS) activate caspase-3 which induces degradation of Ku proteins. In the present study, we investigated the mechanism of b-carotene-induced apoptosis of gastric cancer AGS cells by determining cell viability, DNA fragmentation, apoptotic indices (increases in cytochrome c and Bax, decrease in Bcl-2), ROS levels, mitochondrial membrane potential, caspase-3 activity, Ku70/80 levels, and Ku-DNA-binding activity of the cells treated with or without antioxidant N-acetyl cysteine and caspase-3 inhibitor z-DEVED-fmk. As a result, b-carotene induced apoptosis (decrease in cell viability, increases in DNA fragmentation and apoptotic indices) and caspase-3 activation, but decreased Ku70/80 levels and Ku-DNAbinding activity. b-Carotene-induced alterations (increase in caspase-3 activity, decrease in Ku proteins) and apoptosis were inhibited by N-acetyl cysteine and z-DEVEDfmk. Increment of intracellular and mitochondrial ROS levels and loss of mitochondrial membrane potential were suppressed by N-acetyl cysteine, but not by z-DEVED-fmk in b-carotene-treated cells. Therefore, b-carotene-induced increases in ROS and caspase-3 activity may lead to reduction of Ku70/80 levels, which results in apoptosis in gastric cancer cells. Loss of Ku proteins might be the underlying mechanism for b-carotene-induced apoptosis in gastric cancer cells.

show abstract

β-carotene at high concentrations induces apoptosis by enhancing oxy-radical production in human adenocarcinoma cells

Cited by 113 publications

References 32 publications

Mitogenic and Apoptotic Signaling by Carotenoids: Involvement of a Redox Mechanism

Mitogenic and Apoptotic Signaling by Carotenoids: Involvement of a Redox Mechanism

Redox Regulation by Intrinsic Species and Extrinsic Nutrients in Normal and Cancer Cells

β-Carotene-induced apoptosis is mediated with loss of Ku proteins in gastric cancer AGS cells

Contact Info

Product

Resources

About