This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies.
The green beet (Beta vulgaris var. cicla L.) and red beetroot (B. vulgaris var. rubra L.) contain phytochemicals that have beneficial effects on human health. Specifically, the green beet contains apigenin, vitexin, vitexin-2-O-xyloside and vitexin-2-O-rhamnoside, while the red beetroot is a source of betaxanthins and betacyanins. These phytochemicals show considerable antioxidant activity, as well as antiinflammatory and antiproliferative activities. Vitexin-2-O-xyloside, in combination with betaxanthins and betacyanins, exerts antiproliferative activity in breast, liver, colon and bladder cancer cell lines, through the induction of both intrinsic and extrinsic apoptotic pathways. A significant body of evidence also points to the role of these phytochemicals in the downregulation of the pro-survival genes, baculoviral inhibitor of apoptosis repeat-containing 5 and catenin beta-1, as well as the genes controlling angiogenesis, hypoxia inducible factor 1A and vascular endothelial growth factor A. The multi-target action of these phytochemicals enhances their anticancer activity. Vitexin-2-O-xyloside, betaxanthins and betacyanins can be used in combination with conventional anticancer drugs to reduce their toxicity and overcome the multidrug resistance of cancer cells. In this review, we describe the molecular mechanisms that enable these dietary phytochemicals to block the proliferation of tumor cells and inhibit their pro-survival pathways. Copyright © 2017 John Wiley & Sons, Ltd.
The theory that several carcinogenetic processes are initiated and sustained by cancer stem cells (CSCs) has been validated, and specific methods to identify the CSCs in the entire population of cancer cells have also proven to be effective. This review aims to provide an overview of recently acquired scientific knowledge regarding phytochemicals and herbal extracts, which have been shown to be able to target and kill CSCs. Many genes and proteins that sustain the CSCs’ self-renewal capacity and drug resistance have been described and applications of phytochemicals able to interfere with these signaling systems have been shown to be operatively efficient both in vitro and in vivo. Identification of specific surface antigens, mammosphere formation assays, serial colony-forming unit assays, xenograft transplantation and label-retention assays coupled with Aldehyde dehydrogenase 1 (ALDH1) activity evaluation are the most frequently used techniques for measuring phytochemical efficiency in killing CSCs. Moreover, it has been demonstrated that EGCG, curcumin, piperine, sulforaphane, β-carotene, genistein and the whole extract of some plants are able to kill CSCs. Most of these phytochemicals act by interfering with the canonical Wnt (β-catenin/T cell factor-lymphoid enhancer factor (TCF-LEF)) pathway implicated in the pathogenesis of several cancers. Therefore, the use of phytochemicals may be a true therapeutic strategy for eradicating cancer through the elimination of CSCs.
During the development, progression and dissemination of neoplastic lesions, cancer cells can hijack normal pathways and mechanisms. This includes the control of the function of cellular proteins through reversible post-translational modifications, such as ADP-ribosylation, phosphorylation, and acetylation. In the case of mono-ADP-ribosylation and poly-ADP-ribosylation, the addition of one or several units of ADP-ribose to target proteins occurs via two families of enzymes that can generate ADP-ribosylated proteins: the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family, comprising 17 different proteins that are either poly-ADP-ribosyltransferases or mono-ADP-ribosyltransferases or inactive enzymes; and the clostridial toxin-like ADP-ribosyltransferase family, with four human members, two of which are active mono-ADP-ribosyltransferases, and two of which are enzymatically inactive. In line with a central role for poly-ADP-ribose polymerase 1 in response to DNA damage, specific inhibitors of this enzyme have been developed as anticancer therapeutics and evaluated in several clinical trials. Recently, in combination with the discovery of a large number of enzymes that can catalyse mono-ADP-ribosylation, the role of this modification has been linked to human diseases, such as inflammation, diabetes, neurodegeneration, and cancer, thus revealing the need for the development of specific ARTD inhibitors. This will provide a better understanding of the roles of these enzymes in human physiology and pathology, so that they can be targeted in the future to generate new and efficacious drugs. This review summarizes our present knowledge of the ARTD enzymes that are involved in mono-ADP-ribosylation reactions and that have roles in cancer biology. In particular, the well-documented role of macro-containing ARTD8 in lymphoma and the putative role of ARTD15 in cancer are discussed. The ADP-ribosylation reactionsDuring the development, progression and dissemination of neoplastic lesions, cancer cells can hijack normal intracellular pathways and mechanisms. These can include the pathways involved in intercellular communication, control of transcription, and control of protein localization, function and degradation by Abbreviations ARH, ADP-ribosyl hydrolase; ARTC, clostridial toxin-like ADP-ribosyltransferase; ARTD, diphtheria toxin-like ADP-ribosyltransferase; BAL B-aggressive lymphoma; BRCA1, breast cancer type 1; BRCA2, breast cancer type 2; DLBCL, diffuse large B-cell lymphoma; HDAC2, histone deacetylase 2; HDAC3, histone deacetylase 3; IFN, interferon; IL, interleukin; Kapa, importin a; Kapb1, importin b1/karyopherin b1; mH2A, macro-H2A; PAR, poly-ADP-ribose; PARG, poly-ADP-ribose glycohydrolase; PARP, poly-ADP-ribose polymerase; Stat6, signal transducer and activator of transcription; UPR, unfolded-protein response.
The antiproliferative activity of the XVX + AVNs mixture represents an innovative treatment, which is effective against two types of cancer cells characterized by high resistance to the conventional anticancer drugs.
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