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

Constanze Buhrmann,Olga Golubnitschaja,Peter Kubatka,Mehdi Shakibaei,Alena Liskova,Frank A Giordano,Masoud Najafi,Lenka Koklesova,Dietrich Büsselberg,Marek Samec,Milad Ashrafizadeh,Samson Mathews Samuel,Elizabeth Varghese

doi:10.3390/cancers12092425

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.

Highlights

Cancer is characterized by uncontrolled growth of abnormal cells in the organism
This review focuses on current evidence from both preclinical and clinical research of carotenoids’
Based on data obtained from in vitro and in vivo studies, carotenoids seem to be a good choice for cancer therapy and prevention that have apparent potential to improve the efficacy of conventional treatment or reduce the risk in highly predisposed individuals

Summary

Introduction

Cancer is characterized by uncontrolled growth of abnormal cells in the organism. An initial stage of cancer is irreversible and leads to increased tumor cell proliferation [1]. According to Global Cancer Statistics (GLOBOCAN) 2018, cancer incidence and mortality are rapidly growing worldwide [2]. Carcinogenic factors can be classified into three groups: primary determining factors (chemical substances, physical agents, viruses), secondary determining factors (hereditary determinism), and favoring factors (geographic factors, nutrition, sex, age, etc.). These carcinogenic factors can contribute to cancer development characterized by disturbed cellular homeostasis by hyperplastic, dysplastic or regenerative alterations [3]. Carcinogenesis is commonly associated with DNA damage as a result of exposure to various exogenous (ultraviolet rays, radiation, pollution, smoking, and stress) and endogenous agents (lack of apoptotic function, genetic mutation, oxidative stress, and hypoxia) [4,5]

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