Carcinogenesis is the process whereby a normal cell is transformed into a neoplastic cell. This action involves several steps starting with initiation and followed by promotion and progression. Driving these stages are oxidative stress and inflammation, which in turn encompasses a myriad of aberrant gene expressions, both within the transforming cell population and the cells within the surrounding lesion. Chemoprevention of cancer with bioreactive foods or their extracted/purified components occurs via normalizing these inappropriate gene activities. Various foods/agents have been shown to affect different gene expressions. In this review we discuss whereby the chemoprevention activities of the red beetroot itself may disrupt carcinogenesis and the activities of the water soluble betalains extracted from the plant.

With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes. Our study is the first to investigate the combinatorial effects of low physiologically achievable concentrations of WA and SFN on breast cancer cell proliferation, histone deacetylase1 (HDAC1) and DNA methyltransferases (DNMTs). No adverse effects were observed on control cells at optimal concentrations. There was synergistic inhibition of cellular viability in MCF-7 cells and a greater induction of apoptosis with the combinatorial approach than with either compound administered alone in both MDA-MB-231 and MCF-7 cells. HDAC expression was down-regulated at multiple levels. Lastly, we determined the combined effects of these bioactive compounds on the pro-apoptotic BAX and anti-apoptotic BCL-2 and found decreases in BCL-2 and increases in BAX. Taken together, our findings demonstrate the ability of low concentrations of combinatorial WA and SFN to promote cancer cell death and regulate key epigenetic modifiers in human breast cancer cells.

This study aims to evaluate the factors influencing the adherence to the 2nd and 3rd doses during each cycle of seasonal malaria chemoprevention (SMC) in Burkina Faso, Mali, and Niger. Overall, 3,132 people were interviewed during surveys between 2019 and 2020 in 15 health districts. The median age was 30 years. In Burkina , Mali, and Niger, the proportions of non-adherence were 4.15% , 5.60%, and 13.30%, respectively (95% CI (-3.27% -0.37 %, p = 0.114 ) for the 2nd dose and 3.98%, 5.60% and 14.39% for the 3rd dose. The main cause of non-adherence to the 2nd and 3rd doses was other illnesses in 28.5% and 29.78% respectively in Burkina, 5.35% and 5.35% in Mali and 1.6% and 0.75% in Niger. It was followed by vomiting in 12.24% and 10.63% for Burkina and 2.45% and 3.78% in Niger. The last causes were refusal in 6.12% and 4.25% in Burkina , 33.9% and 15.25% in Mali and 0.8% and 1.51% in Niger. Non-adherence of doses related to parents was primary due to their absence in 28.5% and 27.65% in Burkina , 16.07% and 16.07% in Mali and 7.37 % and 6.06% in Niger. Travelling was the second cause in 12.24 % and 12.76% in Burkina , 19.64% and 19.64% in Mali and 0.81% and 0.75% in Niger. Non-adherence related to community distributors was mainly due to missing of the doses in 4.08% and 4.25% in Burkina , 23.21% and 23.21% in Mali, 77.04% and 76.51% in Niger. Our study reported very small proportions of non-adherence to 2nd and 3rd doses of SMC and identified the main causes of non-adherence.

Zucchini (Cucurbita pepo subsp. pepo) is a seasonal vegetable with high nutritional and medical value. Many useful properties of this fruit are attributed to its bioactive compounds. Zucchini fruits (“Yellow” and “Light Green” varieties) and four distinctive components (lutein, β-carotene, zeaxanthin and dehydroascorbic acid)were selected. Firstly it was determinated the lutein, β-carotene, zeaxanthin and dehydroascorbic acid content in these fruits and then, in order to measure the safety and suitability of their use different assays were carried out: (i) Genotoxicity and antigenotoxicity tests to determine the safety and DNA-protection against hydrogen peroxide; (ii) cytotoxicity and (iii) DNA fragmentation assay to evaluate the proapoptotic effect. Results showed that: (i) all the substances were non-genotoxic, (ii) all the substances were antigenotoxic except the highest concentration of lutein, (iii) “Yellow” Zucchini epicarp and mesocarp exhibited the highest cytotoxic activity (IC₅₀ > 0.1 mg/mL and 0.2 mg/mL, respectively) and iv) “Light Green” Zucchini skin and pulp induced internucleosomal DNA fragmentation . To sump up, Zucchini fruit could play a positive role in human health and nutrition due to this fruit and its components were safe, able to inhibit significantly the H₂O₂-induced damage and exhibit antiproliferative and pro-apoptotic properties toward HL60 tumour cells. The information generated from this research should take into account to select potential accessions for breeding programs purposes.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p<0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16±9.09 μg/mL, 5.96±1.55 μg/mL and 3.05±0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1±63.40 μg/mL and 203.10±17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p<0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p<0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

Green Tea Catechins (GTCs) are a family of chemically related compounds usually classified as antioxidant molecules. Epidemiological evidences, supported by interventional studies, highlighted a more than promising role for GTCs in human Prostate Cancer (PCa) chemoprevention.In the last decades many efforts have been made to gain new insights into the mechanism of action of GTCs. Now it is clear that GTCs anticancer action can no longer be simplistically limited to their direct antioxidant/pro-oxidant properties. Recent contributions to the advancement of knowledge in this field have shown that GTCs specifically interact with cellular targets including, cell surface receptors, lipid rafts and endoplasmic reticulum, modulate gene expression through direct effect on transcription factors or indirect epigenetic mechanisms, interfere with intracellular proteostasis at various levels. Many of the effects observed in vitro are dose and cell context dependent and take place at concentration that cannot be achieved in vivo.Poor intestinal absorption together with an extensive systemic and enteric metabolism influence GTCs bioavailability through still poor understood mechanisms. Recent efforts to develop delivery systems that increase GTCs overall bioavailability, by mean of biopolymeric nanoparticles, represent the main way to translate preclinical results in a real clinical scenario for PCa chemoprevention.

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that arises from the epithelium lining of the oral cavity, hypopharynx, oropharynx, and larynx. Despite advancement of the current treatment to HNSCC, such as surgery, chemotherapy, and radiotherapy, the overall survival rate of HNSCC remains poor due to late diagnosis and acquired resistance to treatment. Natural products have been extensively explored as a safer and more acceptable alternative to current treatments, with numerous studies displaying their potential against HNSCC. This review highlights preclinical studies in the past 5 years involving natural products against HNSCC and explores the signalling pathways altered by these products. This review also addresses challenges and future directions of the use of natural products as chemotherapeutic and chemoprevention agents against HNSCC.

Across different cultures around the globe, human beings have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants can be strongly attributed to the presence of secondary metabolites, particularly polyphenols. The health-promoting effects of Sorghum bicolor supplement Jobelyn® (SBSJ) —a unique supplement derived from the leaf sheaths of a West African variety of Sorghum bicolor (L.) Moench—have also been ascribed to its high levels of polyphenols. This review seeks to gather and synthesize findings from various experimental and clinical studies on the health benefits of SBSJ in arthritis, cancer, chronic viral infections, stroke, anaemia, and aging. SBSJ has been reported to contain potent bioactive polyphenolic compounds with polyvalent biological activities, including antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. Moreover, the probable benefits of SBSJ in chronic viral infections (e.g., HIV/AIDS and COVID-19) have been attributed to its potent anti-inflammatory and immunomodulatory activities. As this supplement is increasingly becoming one of the fastest-selling herbal medicines in Nigeria, there is a need for more robust studies (including clinical trials) in order to replicate and validate the prior insights gleaned from experimental studies.

The purpose of the current study was directed to investigate the effectiveness of docosahexaenoic acid (DHA) as a chemopreventive agent on experimentally induced hamster buccal pouch (HBP) carcinogenesis; Material and methods: 40 Syrian male hamsters, five weeks old, were divided into 4 groups of 10 animals in each as follows, GI: Topical application of liquid paraffin alone (thrice a week for 14 weeks), GII: Topical application of 7, 12 dimethyl benz[a]anthracene (DMBA) alone (0.5 % in liquid paraffin, thrice a week for 14 weeks), GIII: Topical application of DMBA (0.5 % in liquid paraffin, thrice a week for 14 weeks) + Oral administration of DHA (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks on alternative days of DMBA application), GIV : Oral administration of DHA alone (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks); Results: Gross observations and histopathological findings revealed a-GI: normal stratified squamous epithelium b- GII: well and moderately differentiated squamous cell carcinoma (SCC) c-: GIII: showed variable results ranges from hyperkeratosis, hyperkeratosis and focal hyperplasia, mild dysplasia, and well differentiated SCC with superficial invasion of tumor cells not extended to deeper areas d: GIV: normal similar to GI. Immunohistochemical results revealed that oral DHA treatment to DMBA treated hamsters restored the normal expression of bcl-2; Conclusion: DHA has the potential to be a dietary chemopreventive agent due to its capacity to improve carcinogen detoxification and to block/suppress the initiation and promotion stages of experimentally produced HBP carcinogenesis.

Scientific evidence increasingly supports the strong link between diet and health, acknowledging that a well-balanced diet plays a crucial role in preventing chronic diseases such as obesity, diabetes, cardiovascular issues, and certain types of cancer. This perspective opens the door to developing precision diets, particularly tailored for individuals at risk of developing cancer. It encompasses a vast research area and involves the study of an expanding array of compounds with multi-level "omics" compositions, including genomics, transcriptomics, proteomics, epigenomics, miRNomics, and metabolomics. We review here the components of the Southern European Atlantic Diet (SEAD) from both a chemical and pharmacological standpoint. The information sources consulted, complemented by crystallographic data from the Protein Data Bank, establish a direct link between SEAD and its anticancer properties. The data collected strongly suggest that SEAD offers an exceptionally healthy profile, particularly due to the presence of beneficial biomolecules in its foods. The inclusion of olive oil and paprika in this diet provides numerous health benefits, and science supports the anti-cancer properties of dietary supplements with biomolecules sourced from vegetables of the brassica genus. Nonetheless, further research is warranted in this field to gain deeper insights into the potential benefits of SEAD's bioactive compounds against cancer.

Moringa oleifera is a miracle plant with many nutritional and medicinal properties. Chemopreventive value of the combined mixture of moringa leaves and seed residues (MOLSr) at different ratios (M1S9, M1S1 and M9S1) were investigated. MOLSr extracts were subjected to phytochemical screening, antioxidant assays, metabolite profiling and cytotoxic activity on various human cancer cell lines including primary mammary epithelial cells (PMEC). The MOLSr ratio with the most potent antiproliferative activities were used in xenograft mice injected with MDA-MB-231 cell lines for in vivo tumourigenicity study as well as protein and gene expression studies. M1S9, specifically comprised of saponin and amino acid, retained the lowest antioxidant activity and highest glucosinolates content as compared to other ratios. Cell viability decreased significantly in MCF-7 breast cancer cells and PMEC after treatment with M1S9. Solid tumour from MDA-MB-231 xenograft mice was inhibited up to 64.5% at third week after treatment with high-dose M1S9. High-dose M1S9 significantly decreased the expression of calcineurin (CaN) and vascular endothelial cell growth factor (VEGF) proteins as well as the secreted frizzled-related protein 1 (SFRP1) and solute carrier family 39 member 6 (SLC39A6) genes. This study provides new scientific evidence for the chemoprevention properties of MOLSr in breast cancer model.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we performed a mini-meta analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. Mini meta analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling which may be altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we explored whether PAK signaling should be targeted via chemoprevention to reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Systematic literature review provided the effect of anti-diabetic drugs on PAK signaling. Review of clinical studies revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-dependent diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM involves Wnt and G-protein signaling which is altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone is promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Research on retinoid-based cancer prevention, spurred by the effects of vitamin A deficiency on gastric cancer and subsequent clinical studies on digestive tract cancer, unveils novel avenues for chemoprevention. Acyclic retinoids like 4,5-didehydrogeranylgeranoic acid (4,5-didehydroGGA) emerged as potent agents against hepatocellular carcinoma (HCC), distinct from natural retinoids such as all-trans retinoic acid (ATRA). Mechanistic studies reveal GGA's unique induction of pyroptosis, a rapid cell death pathway, in HCC cells. GGA triggers mitochondrial superoxide hyperproduction and ER stress responses through Toll-like receptor 4 (TLR4) signaling and modulates autophagy, ultimately activating pyroptotic cell death in HCC cells. Unlike ATRA-induced apoptosis, GGA and palmitic acid (PA) induce pyroptosis, underscoring their distinct mechanisms. While all three fatty acids evoke mitochondrial dysfunction and ER stress responses, GGA and PA inhibit autophagy, leading to incomplete autophagic responses and pyroptosis, whereas ATRA promotes autophagic flux. In vivo experiments demonstrate GGA's potential as an anti-oncometabolite, inducing cell death selectively in tumor cells and thus suppressing liver cancer development. This review provides a comprehensive overview of the molecular mechanisms underlying GGA's anti-HCC effects and underscores its promising role in cancer prevention, highlighting its importance in HCC prevention.