Can beta-carotene regulate cell growth by a redox mechanism? An answer from cultured cells

Our plain-English summary of Can beta-carotene regulate cell growth by a redox mechanism? An answer from cultured cells, by P. Palozza (Biochimica et Biophysica Acta, 2005).

The study

• Author: P. Palozza
• Journal: Biochimica et Biophysica Acta
• Published: 2005;1740(2):215-21
• Type of article: Review
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Many studies suggest a protective role of beta-carotene against cancer. However, the ATBC and the CARET trials have shown that beta-carotene increases the incidence of lung cancer in heavy smokers and asbestos workers. To explain this paradox, it can be hypothesized that beta-carotene modulates intracellular redox status and through this mechanism, it affects redox-sensitive molecular pathways involved in the regulation of cell cycle progression and apoptosis. Studies conducted in cultured cells seem to confirm such a hypothesis. At low concentrations, the carotenoid may serve as an antioxidant, inhibiting free radical production, while at relatively high concentrations and/or in the presence of a chronic oxidative stress (i.e. smoke), it may behave as a prooxidant, propagating free radical-induced reactions, consuming endogenous antioxidants and inducing DNA oxidative damage. In this context, it may regulate cell growth and death by the modulation of redox-sensitive genes and transcription factors.

In plain English

This article was a review, mainly of the author's own laboratory experiments on cultured cells. It asked whether beta-carotene changes cell growth by altering the oxidation balance inside cells. The aim was to help explain why the ATBC and CARET trials found more lung cancer in heavy smokers and asbestos workers given beta-carotene. In the reviewed studies of colon cancer and leukemia cells, low concentrations of beta-carotene reduced reactive oxygen species and did not change cell growth. High concentrations increased free radicals and slowed growth by inducing programmed cell death (apoptosis). This prooxidant effect occurred at 2.5 to 20 micromolar. In cells exposed to cigarette smoke condensate, beta-carotene increased a marker of oxidative DNA damage even at 0.75 to 4.0 micromolar. These cells, after an initial pause, resumed dividing and did not undergo apoptosis. The author noted that asbestos fibres contain iron and that the CARET trial reported increased lung cancer in asbestos workers, only 38% of whom were current smokers. The author concluded that, in cultured cells, beta-carotene acts as a redox molecule, but stated that these results had been shown only in vitro.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review, mainly of the author's own laboratory's cultured-cell experiments
• Who was studied: Cultured cell lines, not people. They included human colon adenocarcinoma cells (LS-174, WiDr), human leukemia HL-60 cells, RAT-1 immortalized fibroblasts, Mv1Lu lung, MCF-7 mammary and Hep-2 larynx cells, and melanoma cell lines.
• Exposure: Beta-carotene added to cultured cells, alone or together with cigarette smoke condensate (TAR). In some experiments alpha-tocopherol or N-acetylcysteine was also added. Asbestos itself was not tested in the reviewed experiments.
• Main results:
  • In the cultured cancer cells, low concentrations of beta-carotene reduced reactive oxygen species and did not change growth. High concentrations increased free radicals and inhibited growth by inducing apoptosis. The prooxidant effect occurred at concentrations from 2.5 to 20 micromolar.
  • Human leukemia HL-60 cells given 10 to 20 micromolar beta-carotene showed lower reduced glutathione (GSH) and higher oxidized glutathione (GSSG) after 24 hours of treatment.
  • When alpha-tocopherol prevented beta-carotene's prooxidant effects in colon adenocarcinoma and leukemia cells, beta-carotene's effects on cell growth and apoptosis were also lost.
  • In all cell lines treated with cigarette smoke condensate, the increase in the oxidative DNA damage marker 8-OHdG was significantly more pronounced with beta-carotene, even at 0.75 to 4.0 micromolar. Beta-carotene alone increased 8-OHdG only at concentrations above 4.0 micromolar.
  • Cells given smoke condensate plus beta-carotene re-entered the cell cycle after an initial growth arrest and did not undergo apoptosis.
  • Citing other work, the author noted that asbestos fibres contain iron. The author also noted that the CARET trial (another study) reported increased lung cancer in asbestos workers, only 38% of whom were current smokers.
• The authors' conclusion: The author concluded that, in cultured cells, beta-carotene acts as a redox molecule and modulates redox-sensitive pathways involved in cell cycle progression and apoptosis. The author added that this has been shown only in vitro and that knowledge of how it works in living organisms remains incomplete.
• Limitations the authors state:
  • The findings were shown only in cultured cells, and their physiological relevance is controversial and needs to be verified in vivo.
  • How beta-carotene is delivered to cultured cells, and the oxygen level of the environment, may strongly change how it behaves.
  • No cultured cell perfectly replicates the human situation.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Apoptosis, Oxidative Stress.

Related studies

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• Effects of 6-month daily supplementation with oral beta-carotene in combination or not with benzo[a]pyrene on cell-cycle markers in the lung of ferrets — A. Fuster, C. Picó, et al. (2008)
• The enigma of beta-carotene in carcinogenesis: what can be learned from animal studies — R.M. Russell (2004)
• Chemoprevention of cancer: lessons to be learned from beta-carotene trials — H. Vainio (2000)
• beta-Carotene fails to act as a tumor promoter, induces RAR expression, and prevents carcinoma formation in a two-stage model of skin carcinogenesis in male Sencar mice — R.M. Ponnamperuma, Y. Shimizu, et al. (2000)
• No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene — G.L. Ambrosini, A.P. Bremner, et al. (2013)

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