Role of phytochemicals in the chemoprevention of tumors

📝 Abstract

Phytochemicals are plant-derived secondary metabolites, which may exert many biological activities in humans, including anticancer properties. Although recent findings appear to support their role in cancer prevention and treatment, this issue is still controversial. Anti-cancer activity of phytochemicals mainly depends on their multi-target mechanism of action, including antimutagenic, antioxidant and antiproliferative activities. Furthermore, they may modulate the host immune response to cancer, reducing inflammatory microenvironment and enhancing lymphocyte onco-surveillance. Since carcinogenesis is multi-factorial and involves several signaling pathways, multi-targeted agents as phytochemicals may represent promising anticancer compounds. This narrative review aims to analyze the current literature on phytochemicals highlighting their specific targets on carcinogenic molecular pathways and their chemopreventive role. A full comprehension of their activity at molecular and cellular levels will contribute for a better understanding of phytochemical clinical efficacy, thus promoting the identification of new effective plant-derived therapeutics.

💡 Analysis

Phytochemicals are plant-derived secondary metabolites, which may exert many biological activities in humans, including anticancer properties. Although recent findings appear to support their role in cancer prevention and treatment, this issue is still controversial. Anti-cancer activity of phytochemicals mainly depends on their multi-target mechanism of action, including antimutagenic, antioxidant and antiproliferative activities. Furthermore, they may modulate the host immune response to cancer, reducing inflammatory microenvironment and enhancing lymphocyte onco-surveillance. Since carcinogenesis is multi-factorial and involves several signaling pathways, multi-targeted agents as phytochemicals may represent promising anticancer compounds. This narrative review aims to analyze the current literature on phytochemicals highlighting their specific targets on carcinogenic molecular pathways and their chemopreventive role. A full comprehension of their activity at molecular and cellular levels will contribute for a better understanding of phytochemical clinical efficacy, thus promoting the identification of new effective plant-derived therapeutics.

📄 Content

1 Role of phytochemicals in the chemoprevention of tumors Catalano E1 1- Università degli Studi di Bari Aldo Moro, Via Edoardo Orabona, 4, 70126 Bari

Abstract Phytochemicals are plant-derived secondary metabolites, which may exert many biological activities in humans, including anticancer properties. Although recent findings appear to support their role in cancer prevention and treatment, this issue is still controversial. Anti-cancer activity of phytochemicals mainly depends on their multi-target mechanism of action, including antimutagenic, antioxidant and antiproliferative activities. Furthermore, they may modulate the host immune response to cancer, reducing inflammatory microenvironment and enhancing lymphocyte onco- surveillance. Since carcinogenesis is multi-factorial and involves several signaling pathways, multi- targeted agents as phytochemicals may represent promising anticancer compounds. This narrative review aims to analyze the current literature on phytochemicals highlighting their specific targets on carcinogenic molecular pathways and their chemopreventive role. A full comprehension of their activity at molecular and cellular levels will contribute for a better understanding of phytochemical clinical efficacy, thus promoting the identification of new effective plant-derived therapeutics.

1. Introduction

Overwhelming evidence from epidemiological, in vivo, in vitro, and clinical trial data suggests that the plant-based diet can reduce the risk of chronic diseases (e.g., cardiovascular disease, hypertension, diabetes, and cancer) due to presence of biologically active plant compounds or phytochemicals. Phytochemicals include those plant-derived compounds that have specific biological activity in human [1]. They can be defined also as bioactive natural molecules that can be of benefits for human health [2]. In fact single phytochemicals and enriched natural extracts able to interfere with self-renewal and drug resistance pathways in cancer cells were investigated. This is a milestone in the improvement of cancer treatment because the synthetic anticancer drugs that are currently used are often highly toxic for healthy organs and weakens the patient’s immune system.

2 Indeed, in terms of prevention, their beneficial effects have been described in different epidemiological investigations, which underlined, despite the limitations of these kind of studies, a reliable relationship between diets rich in phytochemical and reduction in the risk of developing several diseases, including cancer [3]. Indeed, in particular, high intake of fruits and vegetables, the richest dietary components in phytochemicals, has been correlated to a decrease in the risk of several cancers [4]. Nevertheless, one-third of all cancer deaths is estimated to be preventable by “healthy” lifestyles, including appropriate nutrition [4]. A plethora of phytochemicals, such as carotenoids, antioxidative vitamins, phenolic compounds, terpenoids, steroids, indoles, and fibers, has been considered responsible for the risk reduction [5]. On the other hand, phytochemicals can be assimilated to chemotherapeutics, which are frequently derived from natural substances, directly extracted from plants, or other natural sources, or chemically derived from naturally occurring compounds [2]. Moreover, behind traditional medicine, a large number of cancer patients are currently using plant-derived compounds in the context of complementary therapies [2].
Therefore, a growing interest is arising around phytochemicals role in cancer prevention and treatment. Recent research suggests that the investigation of “new” phytochemicals and related molecular targets can be exploited to identify novel anti-cancer drugs, following sequential steps. This approach consists in the preliminary selection of phytochemical candidates for cancer prevention or therapy, basing on the pre-clinical results related to cell-transformation and anti- tumorigenic activity assays. Phytochemicals need to be further validated by means of in vivo models, determining pharmacokinetics and pharmacodynamic molecular interactions and targets. Clinical trials should assess anti-cancer efficacy, further investigating specific pharmacokinetics and pharmacodynamics in humans. Phytochemicals can contribute to cancer prevention by influencing different stages of the tumor development, from tumor initiation through all the phases of cancer [6], such as cell proliferation, apoptosis, invasion and metastasis, angiogenesis and immortality [7]. From this perspective, this review has the aim to summarize the current body of evidence dealing this particular issue, focusing on specific phytochemicals possessing anticancer properties and their molecular targets, also suggesting new strategies for further biomedical application and future directions.
Phytochemicals anti-cancer properties

Natural phytochemicals were classified a

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