Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine

Abstract

Severe durable changes may occur to the DNA structure caused by exogenous and endogenous risk factors initiating the process of carcinogenesis. By evidence, a large portion of malignancies have been demonstrated as being preventable. Moreover, the targeted prevention of cancer onset is possible, due to unique properties of plant bioactive compounds. Although genoprotective effects of phytochemicals have been well documented, there is an evident lack of articles which would systematically present the spectrum of anticancer effects by phytochemicals, plant extracts, and plant-derived diet applicable to stratified patient groups at the level of targeted primary (cancer development) and secondary (cancer progression and metastatic disease) prevention. Consequently, clinical implementation of knowledge accumulated in the area is still highly restricted. To stimulate coherent co-development of the dedicated plant bioactive compound investigation on one hand and comprehensive cancer preventive strategies on the other hand, the current paper highlights and deeply analyses relevant evidence available in the area. Key molecular mechanisms are presented to detail genoprotective and anticancer activities of plants and phytochemicals. Clinical implementation is discussed. Based on the presented evidence, advanced chemopreventive strategies in the context of 3P medicine are considered.

Keywords: Anti-inflammatory; Antibacterial; Anticancer; Antifungal; Antimutagenic effects; Antioxidant; Beneficiary effects; Biomarkers; Breast cancer; Chemoprevention; Colon cancer; Detoxification; Diet; Exogenous and endogenous agents; Genomic instability; Genoprotection; Genotoxicity; Glutaredoxins; Glutathione; Hydrogen peroxide; Nanoparticles; Nanotechnology; Oncology; Oxidative stress; Phytochemicals; Plant natural substances; Prebiotic; Preclinical and clinical study; Predictive Preventive Personalised Medicine (3PM, PPPM); Probiotic; ROS; Scavanger; Superoxide dismutase; Therapeutic potential; Thioredoxin; Tumour.

Fig. 1

Endogenous and exogenous agents causing DNA damage. Oxidative stress, production of cyclobutane pyrimidine dimers, or carcinogens exposure act as the main initiators of DNA damage. ROS, reactive oxygen species; H₂O₂, hydrogen peroxide; CPDs, cyclobutane pyrimidine dimers; T-T, thymine dimers; HAA, heterocyclic aromatic amines; PAH, polycyclic aromatic hydrocarbons; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; IQ, 2-amino-3-methylimidazo[4,5-f]quinoline; NDMA, N-nitrosodimethylamine; DXR, doxorubicin; MMC, mitomycin C; DES, diethylstilbestrol; ETP, etoposide; MNU/NMU, N-methyl-N-nitrosourea; AOM, azoxymethane; AFB1, aflatoxin B1; IR, ionising radiation; UVA, ultraviolet A; UVB, ultraviolet B; DMBA, 7,12-dimethylbenz[a]anthracene; B[a]P, benzo[a]pyrene

Fig. 2

Antioxidant and detoxifying processes involved in genoprotective activities. Part A demonstrates the metabolic processes of phase I (Cytochrome P450) and phase II (GSTs, NQO1, HO-1) enzymes involved in detoxification of environmental carcinogens. Part B describes the ROS scavenging activity via either enzymatic or non-enzymatic pathways, Nrf2-antioxidant response element signalling pathway, and AhR-dependent pathway. SOD1, superoxide dismutase 1; SOD2, superoxide dismutase 2; SOD3, superoxide dismutase 3; H2O2, hydrogen peroxide; GSH, glutathione; GR, glutathione reductase; GSSG, glutathione disulfide; NADP, nicotinamide adenine dinucleotide phosphate; XO, xanthine oxidase; AhR, aryl hydrocarbon receptor; Nrf2, nuclear factor erythroid 2-related factor 2; KEAP1, Kelch-like ECH-associated protein 1; TRX, thioredoxin; GRX, glutaredoxins; ARE, antioxidant response element; XRE, xenobiotic response element

Fig. 3

Repair mechanisms involved in genoprotective activities. Mutation causes the phosporylation of substrates by ATM and ATR recognising DSBs and SSBs, respectively. SSBs are associated with three different repair mechanisms including NER (TC-NER and GG-NER), BER, and MMR. DSBs can be repaired primarily via error-free HR but in case of defect of HR, error-prone SSA, NHEJ, or MMEJ are involved in repair. ssDNA, single-strand DNA; dsDNA, double-strand DNA; ROS, reactive oxygen species; HR, homologous recombination; SSA, single-strand annealing; MMEJ, microhomology-mediated end joining; NHEJ, non-homologous end joining; MMR, DNA mismatch repair; BER, base excision repair; NER, nucleotide excision repair; ATM, protein kinase ataxia-telangiectasia mutated; ATR, ataxia telangiectasia and Rad3-related protein; OGG1, 8-oxoguanine glycosylase; APE1, human apurinic/apyrimidinic endonuclease 1 Polβ, polymerase β; GG-NER, global genomic nucleotide excision repair; TC-NER, transcription-coupled nucleotide excision repair; XPC, CSA, Cockayne syndrome group A protein; CSB, Cockayne syndrome group B protein; RNAPII, RNA polymerase II; XPA, DNA repair protein complementing xeroderma pigmentosum-A cells; XPG, DNA repair protein complementing xeroderma pigmentosum-G cells; TFIIH, transcription factor II H

Fig. 4

Overview of plant natural substances which are associated with genoprotective abilities in preventive and therapy studies. SO, Salvia officinalis; RWPSs, powdered red wine pomace seasonings; LEO, lemongrass essential oil; CHI, Chrysobalanus icaco; SEE, Sechium edule extract; HIHE, Hemidesmus indicus hydro-alcoholic extract; FCE, Ficus carica leaf extract; BE, Brachystegia eurycoma; AC and AXC, Allium cepa L. and Allium × cornutum; BM, Butea monosperma; WA, withaferin A; ICZ, indolo[3,2-b]-carbazole; EDME, Euphorbia dracunculoides methanol extract; CSME, Crataegus songarica methanol extract; TRCEO/γ-T/p-C, Thymus revolutus Célak essential oil/γ-terpinene/p-cymene; FLAX, flaxseed; MEPPS/PONG/LanB, methanol extract of Pongamia pinnata seeds/pongapin/lanceolatin B; YB, young barley; CB, clove buds; THY, thyme; FPP, fruit peel polyphenols; CIN, cinnamon; vit. C and vit. E, vitamin C (ascorbic acid) and vitamin E (D-α-tocopherol); GTP, green tea polyphenols; A/PFJ, anthocynin/polyphenolic-rich fruit juice; EK, Ethiopian kale (Brassica carinata); EVOO, extra-virgin olive oil; XAN, xanthohumol; SNPs, silver nanoparticles; GA, glycyrrhizic acid; TF, theaflavin; EGCG, epigallocatechine-3-gallate; PLGA, poly (lactide-co-glycolide) acid; TP, tea polyphenols; BSA, bovine serum albumin; APIG, apigenin; SeNPs, selenium nanoparticles