Inhibit Cancer Development Research Articles

Cancer Prevention and Treatment with Polyphenols: Type IV Collagenase-Mediated Mechanisms.

Polyphenols are natural compounds found in many plants and their products. Their high structural diversity bestows upon them a range of anti-inflammatory, anti-oxidant, proapoptotic, anti-angiogenic, and anti-metastatic properties, and a growing body of research indicates that a polyphenol-rich diet can inhibit cancer development in humans. Polyphenolic compounds may modulate the expression, secretion, or activity of compounds that play a significant role in carcinogenesis, including type IV collagenases, such as matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), by suppressing cellular signaling pathways such as nuclear factor-kappa B. These enzymes are responsible for the degradation of the extracellular matrix, thus promoting the progression of cancer. This review discusses the current state of knowledge concerning the anti-cancer activity of polyphenols, particularly curcumin, resveratrol, epigallocatechin-3-gallate, genistein, and quercetin, with a specific focus on their anti-invasive and anti-metastatic potential, based on the most recent in vitro and in vivo studies. It appears that polyphenols may be valuable options for the chemoprevention and treatment of cancer via the inhibition of MMP-2 and MMP-9 and the suppression of signaling pathways regulating their expression and activity.

Blueberry (Vaccinium spp.) Anthocyanins and Their Functions, Stability, Bioavailability, and Applications.

Blueberry fruits are rich in anthocyanins. There are 25 known anthocyanidins found in blueberries (Vaccinium spp.) until now. Anthocyanins found in blueberries have attracted considerable interest for their outstanding abilities as antioxidants, anti-inflammatory agents, anti-diabetic, anti-obesity, and neuroprotection compounds, as well as their potential for preventing cardiovascular diseases, protecting vision, and inhibiting cancer development. However, their application is constrained by issues related to instability and relatively low bioavailability. Thus, this review provides a detailed overview of categories, functions, stability, and bioavailability of blueberry anthocyanins and their practical applications. The available studies indicate that there is more potential for the industrial production of blueberry anthocyanins.

Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling.

The peripheral nervous system is a key regulator of cancer progression. In pancreatic ductal adenocarcinoma (PDAC), the sympathetic branch of the autonomic nervous system inhibits cancer development. This inhibition is associated with extensive sympathetic nerve sprouting in early pancreatic cancer precursor lesions. However, the underlying mechanisms behind this process remain unclear. This study aimed to investigate the roles of pancreatic Schwann cells in the structural plasticity of sympathetic neurons. We examined the changes in the number and distribution of Schwann cells in a transgenic mouse model of PDAC and in a model of metaplastic pancreatic lesions induced by chronic inflammation. Schwann cells proliferated and expanded simultaneously with new sympathetic nerve sprouts in metaplastic/neoplastic pancreatic lesions. Sparse genetic labeling showed that individual Schwann cells in these lesions had a more elongated and branched structure than those under physiological conditions. Schwann cells overexpressed neurotrophic factors, including glial cell-derived neurotrophic factor (GDNF). Sympathetic neurons upregulated the GDNF receptors and exhibited enhanced neurite growth in response to GDNF in vitro. Selective genetic deletion of Gdnf in Schwann cells completely blocked sympathetic nerve sprouting in metaplastic pancreatic lesions in vivo. This study demonstrated that pancreatic Schwann cells underwent adaptive reprogramming during early cancer development, supporting a protective antitumor neuronal response. These finding could help to develop new strategies to modulate cancer associated neural plasticity.

Network Pharmacology Analysis of Liquid-Cultured Armillaria ostoyae Mycelial Metabolites and Their Molecular Mechanism of Action against Gastric Cancer.

Armillaria sp. are traditional edible medicinal mushrooms with various health functions; however, the relationship between their composition and efficacy has not yet been determined. Here, the ethanol extract of liquid-cultured Armillaria ostoyae mycelia (AOME), a pure wild Armillaria sp. strain, was analyzed using UHPLC-QTOF/MS, network pharmacology, and molecular docking techniques. The obtained extract affects various metabolic pathways, such as JAK/STAT and PI3K/AKT. The extract also contains important compounds such as 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl] benzamide, isoliquiritigenin, and 7-hydroxycoumarin. Moreover, the extract targets key proteins, including EGFR, SCR, and IL6, to suppress the progression of gastric cancer, thereby synergistically inhibiting cancer development. The molecular docking analyses indicated that the main compounds stably bind to the target proteins. The final cell culture experimental data showed that the ethanol extract inhibited MGC-803 gastric cancer cells. In summary, our research revealed the beneficial components of AOME for treating gastric cancer and its associated molecular pathways. However, further research is needed to confirm its effectiveness and safety in gastric cancer patients.

Abstract 2795: An investigation to identify the phylogeny of bacterial communities in the pancreatic cancer microbiome by 16SrDNA sequencing and bioinformatic analysis

Abstract The microbiome refers to the diverse community of microorganisms, including bacteria, viruses, fungi, and other microbes, that inhabit various parts of the human body, such as the skin, mouth, gut, and other mucosal surfaces. The role of the microbiome in cancer is a complex and evolving area of research. While much is still being learned, there is evidence suggesting that the microbiome can influence cancer development and progression in several ways. Some bacteria within the microbiome can produce substances that may be either carcinogenic or protective against cancer. For instance, the conversion of certain dietary components by gut bacteria can produce metabolites that may either promote or inhibit cancer development. Different cancers may be associated with specific alterations in the microbiome, for example, the gut microbiome has been extensively studied in relation to colorectal cancer, with certain bacterial species potentially contributing to the development of this cancer. However, the role of microbiome in Pancreatic cancer is still not extensively studied, henceforth, we did a preliminary study to identify novel bacterial communities around pancreatic cancer microbiome by 16SrDNA sequencing in human pancreatic cancer xenograft model mice. Isolating total genomic DNA from the pancreatic model mice feces, 16SrDNA PCR was done using specific primers and the amplicon obtained as PCR product was confirmed by standard DNA gel electrophoresis with a 1 kb standard ladder to be 1.5kb in size universal for all bacterial 16SrDNA. The amplicon was then sent for Next Generation Sequencing at Zymo Research Corporation (CA). The resultant DNA sequences were analyzed by bioinformatics studies and their phylogeny identified by comparing with 16SrDNA data base. Differential abundance of the bacteria’s of the genera Lachnoclostridium, Robinsoniella, Alistipes, Akkermansia and Lactobacillus were observed analyzing the data along with other bacterial communities. We are currently continuing the project to identify more bacterial communities of significance in the pancreatic cancer microbiome and investigating the role and significance of these bacterial communities in pancreatic cancer tumor microenvironment. Acknowledgement This study was done by a joint collaboration between scientists and students of Elizabeth City State University (ECSU) campus of the University of North Carolina Systems and Mayo Clinic, Jacksonville. This research is supported by the NIH-NIGMS grant#T34GM100831-10 to Dr. H. Banerjee and a University of North Carolina General Administration Grant to Dr. Colby Hunter at ECSU. Citation Format: Hirendra N. Banerjee, Colby Hunter, Narendra Banerjee, Karrington Perry, Khadimou Dia, Anasua Banerjee, Santanu Bhattacharya, Hari Krishnareddy Rachamala, Enfang Wang, Shamit Dutta. An investigation to identify the phylogeny of bacterial communities in the pancreatic cancer microbiome by 16SrDNA sequencing and bioinformatic analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2795.

Abstract 4254: Genetically engineered human lung organoid models for lung cancer evolution study

Abstract Initial cellular events in a transitional period from normal to cancer cells, such as transcriptomic or epigenetic dynamics, are poorly understood. Observing these is more challenging than in cancer progression, especially for humans. Mapping this phenomenon in early cancer evolution is crucial, as we can identify targetable molecules to inhibit cancer development at the precancerous stage. Immortalized human cancer cell lines hardly capture these appropriately as they have lost usual cellular characteristics. Normal organoids harbor stem cells and their differentiated cells, reflecting the epithelial physiology of tissues, and are more suitable models for cancer evolution studies. To establish a human cancer development model in vitro, we genetically engineered normal human airway organoids derived from adult stem cells into small cell lung cancer (SCLC). We used CRISPR-Cas9 systems to induce non-homologous end-joining in both TP53 and RB1, the most frequently mutated genes of SCLC. First, we knocked out TP53 of the airway organoids, selected by Nutlin-3a, an MDM2 antagonist, for 3-4 weeks, demonstrating 88-89% editing efficiencies calculated from Sanger sequencing results. Most mutations were one base pair deletion or insertion, which induced frameshift mutation in TP53. They did not show a significant difference from wild-type organoids morphologically at bright-field microscopy. Subsequently, we targeted RB1 on TP53-/- airway organoids to induce SCLC. We used Palbociclib, a CDK4/6 inhibitor, to enrich the mutated cells. They had 67.1% efficiency, and 20.4% had a 7-base pair deletion mutation. In the initial period, they seemed to have similar shapes to TP53-/- organoids. Unexpectedly and interestingly, however, we noticed more rapidly proliferating and disorganized organoids disrupting their original round shapes appeared in 4-5 weeks. The cells were indiscriminately piled up on the airway organoids' apical and basolateral surfaces, indicating their malignant traits. Their chaotic proliferation represented the rapidly progressing clinical feature of SCLC with a median survival of 7-16 months with treatment. This is the first work constructing the SCLC development model from the normal human airway organoid. By sequentially single-cell sequencing this organoid model changing to tumorous condition, we can capture the multi-omics landscape during the initial evolution of SCLC. Citation Format: Sungji Moon, Rokhyun Kim, Dakyung Lee, Kyunghyuk Park, Woochan Lee, Seyoon Lee, Young Jun Park, Jongil Kim. Genetically engineered human lung organoid models for lung cancer evolution study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4254.

MicroRNA-124 plays an inhibitory role in cutaneous squamous cell carcinoma cells via targeting SNAI2, an immunotherapy determinant

PurposeMicroRNAs (miRs) play multiple roles during cutaneous squamous cell carcinoma (CSCC) progression. Previous studies suggest miR-124 could inhibit cancer development in CSCC. Methods: Obtained 63 pairs of CSCC and adjacent tissues for analysis. Cultured HaCaT and two CSCC cell lines (A431 and SCL-1) in DMEM (10 % FBS). Transfected cells using Lipofectamine 2000 with various miR-124 mimics, inhibitors, or Snail family transcriptional repressor 2 (SNAI2) expression plasmid. Performed a series of assays, including real-time quantitative PCR, Western blot, CCK8, wound healing, transwell, and luciferase reporter gene assay, to examine the effects of miR-124 on CSCC cells. Results: An evident downregulation of miR-124 in CSCC tissues, which was related to advanced disease stage and nodal metastasis. Overexpressing miR-124 could reduce the proliferation, migration, and invasion abilities of CSCC cells. It was verified that miR-124 targets the SNAI2 in CSCC cells. Moreover, ectopic expression of SNAI2 rescued the suppressive effects on CSCC cells induced by miR-124 overexpression. Furthermore, miR-124 increased cell sensitivity to cisplatin. Besides, SNAI2 is a critical factor in the immune-related aspects of CSCC and its modulation may influence the response to immunotherapy. Conclusion: We demonstrate that miR-124 inhibits CSCC progression through downregulating SNAI2, and thus it may be a molecular candidate for treating CSCC in the clinic.

Full-atomistic molecular dynamics analysis of p53 active tetramer

p53 is a tumor suppressor protein that plays a crucial role in inhibiting cancer development and maintaining the genetic integrity. Within the cell nucleus, four p53 molecules constitute a stable tetrameric active structure through highly cooperative interactions, bind to DNA via its DNA-binding domain, and transcriptionally activate or inhibit their target genes. However, in most human tumor cells, there are numerous p53 mutations. The majority of these mutations are formed in the p53 DNA-binding domain, importantly, the p53 DNA-binding domain is critical for p53 to form the tetrameric active structures and to regulate the transcription of its downstream target genes. In this work, the all-atom molecular dynamics simulation is conducted to investigate the mechanism of interaction within the wild-type p53 tetramers. This study indicates that the symmetric dimers on either side of the DNA are stable ones, keeping stable structures before and after DNA binding. The binding of two monomers on the same side of the DNA depends on protein-protein interaction provided by two contact surfaces. DNA scaffold stabilizes the tetrameric active structure. Such interactions crucially contribute to the tetramer formation. This study clarifies the internal interactions and key residues within the p53 tetramer in dynamic process, as well as the critical sites at various interaction interfaces. The findings of this study may provide a significant foundation for us to further understand the p53’s anticancer mechanisms, to explore the effective cancer treatment strategies, and in near future, to develop the effective anti-cancer drugs.

Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers.

Resveratrol (RSV), the primary polyphenol found in grapes, has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines, including IL-1β, IL-6, IL-1ra and TNFα. Considering the close association between chronic inflammation and cancer development, RSV's immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation, proliferation, neovascularization, and migration. Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress. In addition to immunomodulation, RSV inhibits cancer development by expressing anti-oxidant effects, causing cell cycle arrest, stimulating the function of certain enzymes, and activating cell signaling pathways. The end outcome is one of the various forms of cell death, including apoptosis, pyroptosis, necroptosis, and more, as it has been observed in vitro. RSV has been shown to act against cancer in practically every organ, while its effects on colon cancer have been documented more frequently. It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol. The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV, with a particular emphasis on cancers of the digestive tract, as a challenge for future clinical research that may contribute to the better prognosis of cancer.

Akkermansia muciniphila - friend or foe in colorectal cancer?

Akkermansia muciniphila is a gram-negative anaerobic bacterium, which represents a part of the commensal human microbiota. Decline in the abundance of A. muciniphila among other microbial species in the gut correlates with severe systemic diseases such as diabetes, obesity, intestinal inflammation and colorectal cancer. Due to its mucin-reducing and immunomodulatory properties, the use of probiotics containing Akkermansia sp. appears as a promising approach to the treatment of metabolic and inflammatory diseases. In particular, a number of studies have focused on the role of A. muciniphila in colorectal cancer. Of note, the results of these studies in mice are contradictory: some reported a protective role of A. muciniphila in colorectal cancer, while others demonstrated that administration of A. muciniphila could aggravate the course of the disease resulting in increased tumor burden. More recent studies suggested the immunomodulatory effect of certain unique surface antigens of A. muciniphila on the intestinal immune system. In this Perspective, we attempt to explain how A. muciniphila contributes to protection against colorectal cancer in some models, while being pathogenic in others. We argue that differences in the experimental protocols of administration of A. muciniphila, as well as viability of bacteria, may significantly affect the results. In addition, we hypothesize that antigens presented by pasteurized bacteria or live A. muciniphila may exert distinct effects on the barrier functions of the gut. Finally, A. muciniphila may reduce the mucin barrier and exerts combined effects with other bacterial species in either promoting or inhibiting cancer development.

The role of the purinergic ligand-gated ion channel 7 receptor in common digestive system cancers.

The incidence of digestive malignancies has increased in recent years, including colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic cancer. Advanced stages of these cancers are prone to metastasis, which seriously reduce the standard of living of patients and lead to decline in the survival rate of patients. So far there are no good specific drugs to stop this phenomenon. It is very important and urgent to find new biomarkers and therapeutic targets. Purinergic ligand-gated ion channel 7 receptor (P2X7R) is ATP-gated and nonselective ion channel receptor involved in many inflammatory processes and cancer progression. P2X7R is present in many cancer cells and promotes or inhibits cancer development through signal transduction. Studies have presented that P2X7R plays a role in the proliferation and migration of digestive system cancers, such as CRC, HCC and pancreatic cancer. Therefore, P2X7R may serve as a biomarker or therapeutic target for digestive system cancers. This paper describes the structure and function of P2X7R, and mainly reviews the research progress on the role of P2X7R in CRC, HCC and pancreatic cancer.

Essential roles of BRD4 in cancer: DNA damage, transcription regulation, and signal transduction

During cancer progression, bromodomain and extra-terminal (BET) families regulate chromatin and recruit enzymes that are associated with chromatin regulation to control gene expression. The bromodomain-containing protein 4 (BRD4) plays an important role in DNA damage repair, nuclear factor kappa B (NFκB) signaling, interaction with c-Myc, and transcription regulation of genes essential in carcinogenesis, as well as links transcription at enhancers and genes to regulate enhancer transcription. The colocalization of BRD4 with enhancer and promoter-proximal gene regions enables the elongation activation at enhancer genes. The inactivation of BRD4 has been demonstrated to inhibit cancer development, corroborating BRD4 as a promising therapeutic target. In addition, small-molecule inhibitors targetting functional domains of BRD4 are under investigation for their potential therapeutic applications in cancer and other diseases. This review presents an overview of BRD4 function and its dysfunction in cancer progression, as well as discusses how the potential of BRD4 as a therapeutic target.

The Role of lncRNA-miR-26a-mRNA Network in Cancer Progression and Treatment.

The role of non-coding RNAs in regulating biological processes associated with cancer progression, such as proliferation, migration, and apoptosis, has been extensively studied. Long non-coding RNAs (lncRNAs) play a role in regulating these processes through various mechanisms, including transcriptional and post-transcriptional modifications. In post-transcriptional regulation, lncRNAs can bind to specific miRNAs and affect their function, which can either promote or inhibit cancer development. The interaction between lncRNAs, miRNAs, and mRNAs forms a network known as competitive endogenous RNA (ceRNA), which is involved in cancer progression or inhibition. One specific miRNA called miR-26a-5p has been identified as having tumor-suppressive properties. However, when lncRNAs bind to and inhibit miR-26a-5p, it can lead to cancer progression. Therefore, targeting this ceRNA network could be a promising strategy for preventing cancer development. This review will first discuss the anticancer effects of miR-26a-5p and then explore the involvement of the lncRNA-miR26a-5p-mRNA axis in cancer progression and potential targeted therapies.

Limonoids from neem (Azadirachta indica A. Juss.) are potential anticancer drug candidates.

Neem (Azadirachta indica A. Juss.), a versatile evergreen tree recognized for its ethnopharmacological value, is a rich source of limonoids of the triterpenoid class, endowed with potent medicinal properties. Extracts of neem have been documented to display anticancer effects in diverse malignant cell lines as well as in preclinical animal models that has largely been attributed to the constituent limonoids. Of late, neem limonoids have become the cynosure of research attention as potential candidate agents for cancer prevention and therapy. Among the various limonoids found in neem, azadirachtin, epoxyazadiradione, gedunin, and nimbolide, have been extensively investigated for anticancer activity. Azadirachtin, a potent biodegradable pesticide, exhibits profound antiproliferative effects by preventing mitotic spindle formation and cell division. The antiproliferative activity of gedunin has been demonstrated to be mediated primarily via inhibition of heat shock protein90 and its client proteins. Epoxyazadiradione inhibits pro-inflammatory and kinase-driven signaling pathways to block tumorigenesis. Nimbolide, the most potent cytotoxic neem limonoid, inhibits the growth of cancer cells by regulating the phosphorylation of keystone kinases that drive oncogenic signaling besides modulating the epigenome. There is overwhelming evidence to indicate that neem limonoids exert anticancer effects by preventing the acquisition of hallmark traits of cancer, such as cell proliferation, apoptosis evasion, inflammation, invasion, angiogenesis, and drug resistance. Neem limonoids are value additions to the armamentarium of natural compounds that target aberrant oncogenic signaling to inhibit cancer development and progression.

Short-chain fatty acids in cancer pathogenesis.

Cancer is a multi-step process that can be viewed as a cellular and immunological shift away from homeostasis in response to selected infectious agents, mutations, diet, and environmental carcinogens. Homeostasis, which contributes importantly to the definition of "health," is maintained, in part by the production of short-chain fatty acids (SCFAs), which are metabolites of specific gut bacteria. Alteration in the composition of gut bacteria, or dysbiosis, is often a major risk factor for some two dozen tumor types. Dysbiosis is often characterized by diminished levels of SCFAs in the stool, and the presence of a "leaky gut," permitting the penetration of microbes and microbial derived molecules (e.g., lipopolysaccharides) through the gut wall, thereby triggering chronic inflammation. SCFAs attenuate inflammation by inhibiting the activation of nuclear factor kappa B, by decreasing the expression of pro-inflammatory cytokines such as tumor necrosis factor alpha, by stimulating the expression of anti-inflammatory cytokines such as interleukin-10 and transforming growth factor beta, and by promoting the differentiation of naïve T cells into T regulatory cells, which down-regulate immune responses by immunomodulation. SCFA function epigenetically by inhibiting selected histone acetyltransferases that alter the expression of multiple genes and the activity of many signaling pathways (e.g., Wnt, Hedgehog, Hippo, and Notch) that contribute to the pathogenesis of cancer. SCFAs block cancer stem cell proliferation, thereby potentially delaying or inhibiting cancer development or relapse by targeting genes and pathways that are mutated in tumors (e.g., epidermal growth factor receptor, hepatocyte growth factor, and MET) and by promoting the expression of tumor suppressors (e.g., by up-regulating PTEN and p53). When administered properly, SCFAs have many advantages compared to probiotic bacteria and fecal transplants. In carcinogenesis, SCFAs are toxic against tumor cells but not to surrounding tissue due to differences in their metabolic fate. Multiple hallmarks of cancer are also targets of SCFAs. These data suggest that SCFAs may re-establish homeostasis without overt toxicity and either delay or prevent the development of various tumor types.

Molecular Docking Study of Bioactive Compounds from Curcuma aeruginosa Roxb. as Antioxidant and Anticancer Activities

Cancer is one type of dangerous disease that is increasing every year. Free radicals are the cause of gene mutations (cancer). Cancer will develop uncontrollably due to the occurrence of the cell cycle and the presence of compounds that trigger cell proliferation and inhibit the process of apoptosis. This cancer treatment is carried out by giving cyclin-dependent kinase2 (CDK2) and cyclooxygenase-2 (COX-2) inhibitor drugs to inhibit cancer development, as well as lipoxygenase (LOX) inhibitor drugs for the formation of free radicals. Curcuma aeruginosa RoxB., the plant, is known to have the potential for antioxidant and anticancer properties. This study aims to determine the molecular interaction between the dominant compound in the ethanol extract of C. aeruginosa with CDK2, COX-2, and LOX receptors. The type of ligand interaction with the receptor was determined through the parameters of affinity energy (∆G), inhibition constant (Ki), type of interaction, and percentage of binding site similarity (%BSS). The results showed that the gajutsulacton A had the best potential in inhibiting CDK2. The cucumenol may be a COX-2 inhibitor, and there are no compounds that can inhibit LOX as well as an antioxidant. Thus, our findings demonstrate the potential for C. aeruginosa bioactive to serve as anticancer candidate molecules against CDK2 and COX-2 receptors.

Inhibition of Cancer Development by Natural Plant Polyphenols: Molecular Mechanisms.

Malignant tumors remain one of the main sources of morbidity and mortality around the world. A chemotherapeutic approach to cancer treatment poses a multitude of challenges, primarily due to the low selectivity and genotoxicity of the majority of chemotherapeutic drugs currently used in the clinical practice, often leading to treatment-induced tumors formation. Highly selective antitumor drugs can largely resolve this issue, but their high selectivity leads to significant drawbacks due to the intrinsic tumor heterogeneity. In contrast, plant polyphenols can simultaneously affect many processes that are involved in the acquiring and maintaining of hallmark properties of malignant cells, and their toxic dose is typically much higher than the therapeutic one. In the present work we describe the mechanisms of the action of polyphenols on cancer cells, including their effects on genetic and epigenetic instability, tumor-promoting inflammation, and altered microbiota.

Testing the Anticancer Effect of Matcha Using Zebrafish as an Animal Model.

Cancer is the second leading cause of death worldwide, and triple-negative breast cancer (TNBC) patients show the poorest prognosis and survival and the highest metastasis prevalence among all breast cancer subtypes. Matcha has recently been associated with multiple health benefits, and in vitro studies showed the potential effect of matcha in inhibiting cancer development and metastasis. We aimed to determine the safe, non-toxic dose of matcha suitable for zebrafish and to investigate the anticancer effect of matcha on the metastasis and growth of human TBNC cells using a zebrafish xenograft model. Wild-type AB zebrafish were used to conduct multiple general toxicity assessments, including developmental, neuromuscular, and cardiovascular toxicities. The safe, non-toxic concentration of matcha was determined to be 50 µg/mL and 100 µg/mL. Afterward, the zebrafish xenograft model was successfully established for MDA-MB-468 and MDA-MB-231 TNBC cells. The tumor size and metastasis of the injected cancer cells were traced through CM-Dil red fluorescent dye. Upon exposure to matcha at the safe doses, MDA-MB-231 and MDA-MB-468 showed a trend toward reduction in tumor size in a dose-dependent manner, indicated by quantified fluorescence. Matcha also visibly suppressed metastasis of cancer cells in the zebrafish body. Our results point to a potential dose-dependent anticancer effect of matcha on TNBC cells; however, more extended observation periods after xenotransplantation are required to confirm the long-term anticancer effect of matcha on tumor growth and metastasis.

The Plausible Use of Mango (Mangifera indica) Peel Isoquercitrin as Adjuvant Therapy for Colorectal Cancer: Translating Research from Bench to Bedside

A deadly and debilitating disease, colorectal cancer (CRC), is rapidly becoming a significant threat to public health. However, current therapeutic approaches are still hampered by various side effects. Due to its benefits and remarkable apoptotic impact on cancer cells, plant-derived flavonoids now garner interest as candidates for cancer therapy. Isoquercitrin, a flavonoid commonly found in fruit plants, especially mangoes, is notable due to its ability to inhibit cancer development through various mechanisms. This review aims to highlight the use of isoquercitrin extracted from mango peels in inhibiting CRC carcinogenesis. A literature search was done on Pubmed, Proquest, and Google Scholar using inclusion and exclusion criteria, and a narrative review was synthesised using the evidence gathered. Validity assessment was done through the the Office of Health Assessment and Translation (OHAT) and Oxford Center for Evidence-Based Medicine (CEBM) critical assessment tools. Evidence suggested that isoquercitrin is promising as adjuvant therapy in CRC. It may inhibit overaccumulation of cytoplasmic β-catenin and its translocation into the nucleus, thus downregulating the expression of target proto-oncogenes leading to carcinogenesis of colon crypts. Isoquercitrin concentration in mango peel is abundant, 557.7 mg/kg in dried mango peel and 31.0 mg/kg in pure extracts. A pharmacology study approved that a daily intake of 5.4 mg/kgBW of isoquercitrin has an effective anticancer effect. This substance has good oral bioavailability and is well-tolerated but inhibits the metabolising enzymes CYP1A1 and CYP1B1. In conclusion, isoquercitrin is a potential adjuvant in inhibiting CRC growth with minimum costs and side effects.

Association between first-step analgesic use and cancer in patients with diabetes.

This study aimed to determine the effectiveness of analgesics in inhibiting cancer development in patients with diabetes based on a sample cohort supplied by the Korean National Health Insurance Service. Regular users of analgesics included those using prescription analgesics ≥15 days per month at least 6 times over 2 years after the diagnosis of diabetes mellitus (baseline). The effectiveness of analgesics in patients with diabetes was evaluated using metformin adherence and three models: model 1 was adjusted for age and sex; model 2 was further adjusted for body mass index (BMI), exercise, cholesterol, hypertension, and Charlson comorbidity index (CCI); and model 3 was further adjusted for analgesics. Based on stringent extraction criteria, the sample had a cancer incidence of 4.6%. The hazard ratios of models 1 and 2 were 0.830 and 0.865, respectively. The adjusted hazard ratio for all variables, including acetaminophen and nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen, was 0.871 (model 3). Regular use of analgesics by patients with diabetes decreased their risk of subsequent cancer development in this large national cohort. Compared with participants who did not develop cancer, those with cancer were older and more likely to be male, did not exercise, have more comorbidities (as assessed by CCI), and did not use analgesics regularly.