Beta-carotene, a vital natural pigment abundant in vegetables and fruits, boasts antioxidants, cell gap junction, and immune functions. Its diverse roles make it a potential preventive and therapeutic agent for various chronic diseases, notably gastric cancer-a high-incidence malignancy with complex etiology.
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Introduction of Beta-Carotene
Beta-carotene, a major category within the carotenoid family, stands out for its vibrant orange-red hue and exceptional nutritional activity. The chemical structure of beta-carotene reveals its unique features. Composed of 40 carbon atoms and 56 hydrogen atoms (C40H56), beta-carotene forms a cyclic structure at both ends of the molecule. The central feature is an extensive system of double bonds and single bonds, with 11 conjugated double bonds, two of which are located on the ring. This structural arrangement contributes to the compound's hydrophobic nature, making it easily dispersible in lipid phases. Beta-carotene's hydrophobicity, coupled with its stability, renders it a valuable natural pigment for various applications, particularly in the food industry.
Fig. 1 Structure of beta-carotene (Chen Q. H, et al. 2021).
Functions of Beta-Carotene
Antioxidant Powerhouse
At the core of beta-carotene's significance lies its role as a potent antioxidant. Antioxidants are essential in neutralizing reactive oxygen species (ROS), which play a pivotal, albeit double-edged, role in physiological and pathophysiological processes. Beta-carotene's ability to scavenge ROS contributes to the reduction of oxidative stress and prevents oxidative damage to vital cellular components, including DNA.
In the intricate dance of molecular oxygen utilization within aerobic organisms, the formation of ROS is inevitable. Carotenoids, and beta-carotene in particular, act as effective antioxidants, inhibiting the expression of NADPH oxidase subunits and increasing the activity of antioxidant enzymes. The consequence is a reduction in lipid peroxidation, protecting nucleic acids, proteins, cell membranes, and cells from the deleterious effects of oxidative stress.
However, the relationship between beta-carotene and oxidative stress is nuanced. While low concentrations of beta-carotene exhibit protective antioxidant activity, higher concentrations may paradoxically display pro-oxidant effects. The delicate balance between the concentration of beta-carotene and its impact on cellular processes underscores the need for precise understanding in harnessing its benefits.
Influence on Gap Junctional Intercellular Communication (GJIC)
Gap junctions, critical components in the cellular landscape, facilitate intercellular communication by forming channels between adjacent cells. Beta-carotene has been implicated in modulating Gap Junctional Intercellular Communication (GJIC), a process vital for the exchange of ions and small molecules between cells.
Studies indicate that beta-carotene exerts protective effects on H2O2-induced inhibition of GJIC in specific cell lines. This modulation involves the restoration of connexin 43 (Cx43) mRNA expression and the prevention of Cx43 protein phosphorylation. The regulatory effects of beta-carotene on connexin expression suggest its potential influence on cellular communication, further highlighting its multifaceted impact.
Immune System Activation
Beta-carotene emerges as a key player in immune system modulation, showcasing its potential to activate immune responses. In studies focusing on the effective components of certain plants, beta-carotene demonstrated the ability to activate spleen cells and macrophages. This immune-enhancing effect is attributed to the activation of nuclear factor kappa-B (NF-κB) pathways and the stimulation of immune cells producing Th1 cytokines.
Beyond its role in enhancing immune responses, beta-carotene showcases therapeutic potential in the context of cancer. Studies suggest that beta-carotene can inhibit M2 macrophage polarization and fibroblast activation, providing a potential avenue for intervention in colorectal cancer. Additionally, beta-carotene's influence on macrophage phagocytosis further underscores its multifaceted role in immune function.
Precursor to Vitamin A and Essential Nutrient
Beta-carotene's significance extends beyond its individual functions as it serves as the most abundant dietary precursor to vitamin A. Vitamin A, essential for normal embryonic development in mammals, is enzymatically derived from beta-carotene in the intestinal mucosa.
The provitamin A role of beta-carotene positions it as a critical nutrient for sustaining various physiological processes. Its conversion to vitamin A, coupled with its antioxidant and immune-modulating properties, makes beta-carotene an indispensable component of a health-supporting diet.
The Mechanism by Which Beta-Carotene Modulates Gastric Cancer
Cell Cycle Regulation
Beta-carotene demonstrates a remarkable influence on the cell cycle of gastric cancer cells. Studies reveal that the reduction in Ku70/80 levels, crucial DNA binding regulatory subunits, is linked to the apoptosis of gastric adenocarcinoma cells. Beta-carotene-induced increases in ROS levels and caspase-3 activity contribute to Ku protein loss, suggesting a potential mechanism for the apoptosis of gastric cancer cells.
Additionally, beta-carotene's impact on ataxia-telangiectasia-mutated (ATM), a sensor for DNA-damaging agents, underscores its role in apoptosis induction. By increasing the levels of apoptotic protein p53 and decreasing antiapoptotic protein Bcl-2 and nuclear ATM, beta-carotene contributes to the apoptosis of gastric cancer cells.
Oxidative Stress Reduction
Beta-carotene's role in mitigating oxidative stress in gastric cancer cells is evident in various in vitro experiments. The inhibition of lipid peroxidation, reduction in interleukin-8 production, and suppression of NF-κB activation showcase beta-carotene's antioxidative properties.
Importantly, under acidic conditions mimicking the gastric environment, beta-carotene's ability to scavenge lipid peroxyl radicals provides a protective mechanism. This inhibition of lipid peroxidation contributes to the prevention of oxidative stress-mediated gastric inflammation, presenting beta-carotene as a potential ally in maintaining gastric health.
Inhibition of Signaling Pathways
Beta-carotene's influence on key signaling pathways implicated in cancer progression further elucidates its potential in modulating gastric cancer. The unique proline isomerase Pin1, crucial for proline-directed phosphorylation, is inhibited by ATRA (all-trans retinoic acid), a derivative of vitamin A. Beta-carotene's conversion to ATRA positions it as an inhibitor of Pin1, thereby blocking multiple cancer-driving pathways such as PI3K/AKT and Wnt/β-catenin signaling.
Additionally, beta-carotene disrupts the Notch pathway, a key player in gastric cancer development. Studies demonstrate that beta-carotene suppresses Notch1 and Hes1 expression, impeding the progression of gastric cancer cells. The intricate interplay between beta-carotene and signaling pathways highlights its potential to target multiple facets of gastric cancer development.
Suppression of β-Catenin Signaling
Beta-carotene's influence on the Wnt/β-catenin signaling pathway is a focal point in understanding its impact on gastric cancer. Studies reveal that beta-carotene inhibits the nuclear translocation of β-catenin, a critical step in Wnt pathway activation. By suppressing β-catenin signaling, beta-carotene impedes the proliferation and survival of gastric cancer cells, presenting a compelling mechanism for its anticancer effects.
The disruption of the Wnt/β-catenin pathway by beta-carotene is associated with the downregulation of cyclin D1 and c-myc, both key players in cell cycle regulation. The modulation of these downstream effectors further solidifies beta-carotene's role in arresting the cell cycle and preventing uncontrolled cell proliferation.
Conclusion
Beta-carotene, celebrated for its vibrant color in the world of carotenoids, unveils a myriad of functions that extend beyond visual appeal. Its antioxidant prowess, role in cellular communication, immune modulation, and intricate influence on signaling pathways position it as a potential guardian against gastric cancer. As ongoing research unravels the complexities of beta-carotene's mechanisms, a clearer understanding of its role in gastric cancer prevention emerges, offering hope in the fight against this formidable disease.
Reference
- Chen Q. H., et al. Beta-carotene and its protective effect on gastric cancer. World Journal of Clinical Cases. 2021, 9(23): 6591.
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