Carotenoids in Cancer Apoptosis—The Road from Bench to Bedside and Back

Abstract

An incidence and mortality of cancer are rapidly growing worldwide, especially due to heterogeneous character of the disease that is associated with irreversible impairment of cellular homeostasis and function. Targeting apoptosis, one of cancer hallmarks, represents a potent cancer treatment strategy. Carotenoids are phytochemicals represented by carotenes, xanthophylls, and derived compounds such as apocarotenoids that demonstrate a broad spectrum of anti-cancer effects involving pro-apoptotic signaling through extrinsic and intrinsic pathways. As demonstrated in preclinical oncology research, the apoptotic modulation is performed at post-genomic levels. Further, carotenoids demonstrate additive/synergistic action in combination with conventional oncostatic agents. In addition, a sensitization of tumor cells to anti-cancer conventional treatment can be achieved by carotenoids. The disadvantage of anti-cancer application of carotenoids is associated with their low solubility and, therefore, poor bioavailability. However, this deficiency can be improved by using nanotechnological approaches, solid dispersions, microemulsions or biofortification that significantly increase the anti-cancer and pro-apoptotic efficacy of carotenoids. Only limited number of studies dealing with apoptotic potential of carotenoids has been published in clinical sphere. Pro-apoptotic effects of carotenoids should be beneficial for individuals at high risk of cancer development. The article considers the utility of carotenoids in the framework of 3P medicine.

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

“…In addition, several epigenetic molecular mechanisms, including DNA methylation patterns (i.e., hypermethylation of tumor-suppressor genes and hypomethylation of oncogenes), improper posttranslational histone chemical modifications, and the aberrant modulation in expression of microRNA, represent important drivers of carcinogenesis [ 3 ]. Spanning several decades, preclinical research has provided emerging evidence pertaining to the beneficial action of phytochemicals and whole plant foods on multiple cancer-related biological pathways [ 4 , 5 , 6 , 7 , 8 , 9 ]. Despite extensive preclinical research, only a limited number of clinical meta-analyses and epidemiological studies have described that long-term (several years) and regular (4–5 times a week) consumption of whole plant foods significantly decreases the risk of breast cancer [ 10 , 11 , 12 , 13 ].…”

Carotenoids in Cancer Metastasis—Status Quo and Outlook

“…The primary health benefits of carotenoids are based on their antioxidant activity [ 80 ]. Moreover, as discussed in our previous review, carotenoids exert positive effects on human health, especially in disease prevention and health maintenance, not only through their antioxidant effects but also through anti-inflammatory effects and enhancement of the immune system [ 20 ]. Over the past two decades, carotenoids’ potential roles in carcinogenesis, in both cancer prevention and therapy, were established [ 81 , 82 ].…”

“…Carotenoids can be classified into two groups according to the presence or absence of oxygen in their molecules. Hydrocarbon carotenoids without oxygen in their molecules, such as α-carotene, β-carotene, and lycopene, are collectively called carotenes, which are commonly found in the human diet [ 20 , 83 ].…”

“…Xanthophylls are the naturally occurring oxygenated derivatives of hydrocarbon carotenoids, commonly synthesized by plants and microorganisms. Major xanthophylls in the human diet, including lutein, zeaxanthin, and β-cryptoxanthin, and xanthophylls found in bacteria, yeast, and algae, including astaxanthin and fucoxanthin, exert anti-cancer properties [ 20 , 95 ].…”

“…Carotenoids are liposoluble pigments often present in orange, yellow, or red vegetables and fruit, as well as fungi, bacteria, and algae [ 16 , 17 ]. Carotenoids have various biological, especially oncologic, effects [ 18 , 19 , 20 ]. Thus, 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).…”