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Review
. 2024 Aug 30;13(9):1060.
doi: 10.3390/antiox13091060.

The Antitumour Mechanisms of Carotenoids: A Comprehensive Review

Andrés Baeza-Morales  1 , Miguel Medina-García  1 , Pascual Martínez-Peinado  1 , Sandra Pascual-García  1 , Carolina Pujalte-Satorre  1 , Ana Belén López-Jaén  1 , Rosa María Martínez-Espinosa  2   3 , José Miguel Sempere-Ortells  1
Affiliations
Review

The Antitumour Mechanisms of Carotenoids: A Comprehensive Review

Andrés Baeza-Morales et al. Antioxidants (Basel). .

Abstract

Carotenoids, known for their antioxidant properties, have garnered significant attention for their potential antitumour activities. This comprehensive review aims to elucidate the diverse mechanisms by which carotenoids exert antitumour effects, focusing on both well-established and novel findings. We explore their role in inducing apoptosis, inhibiting cell cycle progression and preventing metastasis by affecting oncogenic and tumour suppressor proteins. The review also explores the pro-oxidant function of carotenoids within cancer cells. In fact, although their overall contribution to cellular antioxidant defences is well known and significant, some carotenoids can exhibit pro-oxidant effects under certain conditions and are able to elevate reactive oxygen species (ROS) levels in tumoural cells, triggering mitochondrial pathways that would lead to cell death. The final balance between their antioxidant and pro-oxidant activities depends on several factors, including the specific carotenoid, its concentration and the redox environment of the cell. Clinical trials are discussed, highlighting the conflicting results of carotenoids in cancer treatment and the importance of personalized approaches. Emerging research on rare carotenoids like bacterioruberin showcases their superior antioxidant capacity and selective cytotoxicity against aggressive cancer subtypes, such as triple-negative breast cancer. Future directions include innovative delivery systems, novel combinations and personalized treatments, aiming to enhance the therapeutic potential of carotenoids. This review highlights the promising yet complex landscape of carotenoid-based cancer therapies, calling for continued research and clinical exploration.

Keywords: antioxidant activity; antitumour; apoptosis; carotenoid; cell proliferation; metastasis inhibition; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Structure and classification of the most studied carotenoids in cancer. Carotenoids are divided into two main groups, xanthophylls and carotenes. These can also undergo modifications and generate new carotenoids called apocarotenoids. Hydroxyl groups are represented in red. Chemical structures obtained from ChemSpider (Royal Society of Chemistry).
Figure 2
Figure 2
Scheme of the pro-oxidant carotenoid therapy against cancer. Carotenoids exert pro-oxidant effects to selectively target cancer cells, promoting oxidative stress-induced cell death while potentially protecting normal cells. CAR, carotenoid; ROS, reactive oxygen species. Created with BioRender.com.
Figure 3
Figure 3
Scheme of direct antitumoural effects of carotenoids on cancer cells. Carotenoids can induce apoptosis, necroptosis, autophagy or cell differentiation; enhance gap junctional communication; and also exhibit antiangiogenic, antimetastatic, multidrug resistance and antiproliferative effects. CAR, carotenoids. Created with BioRender.com.
Figure 4
Figure 4
Mechanism of action of the anticancer properties of carotenoids. Graphical representation of the most common mechanisms of action of carotenoids in tumour cells based on the reviewed literature. Arrows with pointed ends indicate activation, while T-bar arrows indicate inhibition. ΔΨm, membrane potential; Akt, protein kinase B; Bax, Bcl-2-associated X-protein; Bcl-2, B-cell lymphoma 2 protein; CAR, carotenoid; CDK, cyclin-dependent kinases; GADD45α, growth arrest and DNA-damage-inducible protein 45 α; MMP, matrix metalloproteinase; NF-κB, nuclear factor-kappa B; PARP, poly ADP-ribose polymerase; ROS, reactive oxygen species; SKP2, S-phase kinase-associated protein 2. Created with BioRender.com.
Figure 5
Figure 5
Chemical structure and formulation of bacterioruberin and its derivatives. Bacterioruberin can be modified and converted into bisanhydrobacterioruberin, monoanhydrobacterioruberin or 2-isopentenyl-3,4-dehydrorhodopin. Hydroxyl groups are represented in red. Chemical structures obtained from ChemSpider (Royal Society of Chemistry).
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