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.

Carotenoids are lipophilic pigments naturally occurring in plants and, to a lesser extent, in certain non-photosynthetic organisms. They play a critical role in human health due to their antioxidant and immunomodulatory properties. Key carotenoids such as β-carotene, lycopene, lutein, and zeaxanthin are capable of neutralizing reactive oxygen species, thereby mitigating oxidative stress—a major contributor to the onset and progression of chronic diseases. These compounds also modulate immune responses by influencing lymphocyte proliferation, enhancing natural killer cell activity, and regulating the production of pro- and anti-inflammatory cytokines. Such immunomodulatory effects are associated with a reduced risk of infectious diseases and have shown potential protective roles against inflammatory conditions, cardiovascular and neurodegenerative disorders, and certain types of cancer. Moreover, diets rich in carotenoids are linked to improved immune status, particularly in vulnerable populations such as the elderly and immunocompromised individuals. Despite strong epidemiological evidence, clinical trials involving carotenoid supplementation have produced mixed results, indicating that their effectiveness may depend on the broader dietary context and interactions with other nutrients. In summary, carotenoids are important dietary compounds that contribute to immune regulation and the prevention of various diseases, although further clinical research is needed to determine optimal intake levels and assess their full therapeutic potential.

Mesenchymal stem cells (MSC) are a widely used population in cell therapy for their ability to differentiate into distinct tissues and more lately, for their immunomodulatory properties. However, the use of heterogeneous populations could be responsible for the nondesired outcomes reflected in the literature. Here, we analyse the different capacities of five one-cell-derived MSC clones to exert their immunomodulation ex vivo. We assessed proliferation assays in cocultures of MSC clones and purified cluster of differentiation (CD)3⁺, CD4⁺, or CD8⁺ lymphocytes; analysed the regulatory T (Treg) cells fold change rate; determined the effects on viability of peripheral blood mononuclear cells (PBMC); and also measured the coculture cytokine profiles (Th1/Th2). Conditioned media (CM) of different clones were also used to perform both proliferation assays and to analyse Treg fold change. The five clones analysed in this work were able to generate heterogeneous environments. Different clones inhibited proliferation of CD3⁺ and CD4⁺ lymphocytes, with different intensities. Surprisingly, all clones promoted proliferation of CD8⁺ lymphocytes. Different MSC clones and their CM were able to increase the number of Treg with different intensities. Finally, different clones also promoted different effects on the viability of PBMC treated with ultraviolet light. Considering all these data together, it seems that different clones, even from the same donor, can promote a wide spectrum of responses from anti-inflammatory to proinflammatory character. This fact may be important to standardise the design of personalized cell therapy protocols, thus diminishing the aforementioned undesired outcomes existing nowadays in this type of therapies.