Abstract
Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial–mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients.
Highlights
Metastasis is a complex process involving the formation of secondary tumors adjacent to or distant from the primary cancer site
In MDA-MB-157 and MCF-7 breast cancer cells under hydrogen peroxide-induced hypoxic conditions, lutein treatment modulated the expression of EMT-associated factors and reduced NOTCH signaling associated with the inhibition of tumor invasion and migration
All data mentioned in this review strongly suggest that different groups of carotenoids may target multiple molecular signaling pathways associated with metastatic cancer
Summary
Metastasis is a complex process involving the formation of secondary tumors adjacent to or distant from the primary cancer site. The prevention or early diagnosis of cancer certainly improves clinical outcomes [5], cancer is diagnosed frequently in advanced stages associated with metastasis [6]. In this review, we discuss the potentially beneficial effects of carotenoids through the modulation of multistep metastatic processes and the regulation of multiple signaling pathways and molecules associated with metastasis (e.g., epithelial–mesenchymal transition (EMT), tumor microenvironment, extracellular matrix (ECM), genetic and epigenetic factors, cancer stem cells (CSCs), and chronic inflammation). We highlight the anti-cancer effects of carotenoids in the modulation of metastatic processes, as evaluated primarily in preclinical studies. An accurate evaluation of carotenoids’ applicability in metastatic cancer patients, either as individual compounds or in combination with other therapeutics, could lead to the identification of novel agents to improve the treatment outcomes of advanced cancer patients
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