Cited by 173Antioxidant Activity and Oxidative StressCancer and biochemical researchCell death mechanisms and regulation

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Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

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Shin, Juhyun, Song, Min-Ho, Oh, Jae-Wook, Keum, Young-Soo, Saini, Ramesh Kumar·2020·Antioxidants

DOI 10.3390/antiox9060532PMC PMC7346220

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Abstract

Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the pro-oxidant function of several common dietary carotenoids, including astaxanthin, β-carotene, fucoxanthin, and lycopene, has been investigated for their effective killing effects on various cancer cell lines. Besides, when carotenoids are delivered with ROS-inducing cytotoxic drugs (e.g., anthracyclines), they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants. These dynamic actions of carotenoids can optimize oxidative stress in normal cells while enhancing oxidative stress in cancer cells. This review discusses possible mechanisms of carotenoid-triggered ROS production in cancer cells, the activation of pro-apoptotic signaling by ROS, and apoptotic cell death. Moreover, synergistic actions of carotenoids with ROS-inducing anti-cancer drugs are discussed, and research gaps are suggested.

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Figure 1 An outline of major differences in cellular metabolism between normal and cancer cells. Under pre-existence conditions of high oxidative stress in cancer cells, carotenoids predominantly function as pro-oxidants, resulting in the ROS-triggered apoptosis of cancer cells.CC BY · PubMed Central

Figure 2 Possible routes of carotenoids-triggered reactive oxygen species (ROS) production in cancer cells.CC BY · PubMed Central

Figure 3 Key pro-apoptotic and anti-apoptotic factors regulated by enhanced reactive oxygen species (ROS) levels, mediated by pro-oxidant effects of carotenoids. Bcl-2: B-cell lymphoma 2; Bak: Bcl-2 homologous antagonist/killer; Bax: Bcl-2-associated X protein; Bcl-xL: Bcl-extra-large; Bim: Bcl-2-like protein 11; NF-kB: Nuclear factor-κB; PARP: poly (ADP-ribose) polymerase.CC BY · PubMed Central

Figure 4 Major routes of p53 activation triggered by carotenoids-mediated reactive oxygen species (ROS)-induced. (A) E3 ubiquitin ligases MDM2 and MDM4 mediated proteasomal degradation in non-stress cells; (B) Kinases-mediated activation in cancer cells, and (C) Direct redox activation by S-glutathionylation of redox-sensitive cysteine residues at 124, 135, 141, and 277 of DNA-binding domain. ATM: ataxia telangiectasia mutated; ATR: ataxia telangiectasia and Rad3 related (a serine/threonine-protein kinase); DNA-PK: DNA-dependent protein kinase.CC BY · PubMed Central

Figure 5 Mechanisms of the carotenoids-mediated p53-induced apoptosis of cancer cells. Bcl-2: B-cell lymphoma 2; Bad: Bcl-2-associated agonist of cell death; Bak: Bcl-2 homologous antagonist/killer; Bax: Bcl-2-associated X protein; Bcl-xL: Bcl-extra-large; Bid: BH3 interacting-domain death agonist; Bim: Bcl-2-like protein 11; Noxa: Latin for damage, also known as phorbol-12-myristate-13-acetate-induced protein PMAIP1; PARP: poly (ADP-ribose) polymerase.CC BY · PubMed Central

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Authors: Shin, J., Song, M.-H., Oh, J.-W., Keum, Y.-S., & Saini, R. K.
Affiliations: Konkuk University (KR)
Department of Crop Science, Konkuk University, Seoul 143-701, Korea
Corresponding author: Saini, Ramesh Kumar
ORCID: Shin, Juhyun
Oh, Jae-Wook
Keum, Young-Soo
Saini, Ramesh Kumar
Venue: Antioxidants
Publisher: MDPI AG
Published: 2020-06-17
Volume: 9
Issue: 6
Pages: 532
ISSN: 2076-3921 (ISSN-L)
DOI: 10.3390/antiox9060532
PMC: PMC7346220
OpenAlex: W3036006354
Cited by: 173
References: 67
Citations by year: 2026: 18 · 2025: 25 · 2024: 30 · 2023: 32 · 2022: 33 · 2021: 28 · 2020: 7
FWCI: 2.19
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Antioxidants (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Research Foundation of Korea (2019R1G1A1006815)
Topics: Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: carotenoids, pro-oxidant activity, reactive oxygen species, apoptosis, cancer cells, astaxanthin, beta-carotene, fucoxanthin, lycopene, anthracyclines, oxidative stress, pro-apoptotic signaling, drug synergy, dietary carotenoids

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Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

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