Inhibition Of Carcinogenesis Research Articles

Assessment of in vivo and in vitro anti-tumoral effects of Lycium barbarum extract on Ehrlich ascites tumor cells: histopathology, DNA damage and AgNOR.

Natural product research has an exciting and glorious past that spans over millennia. Accordingly, natural products mediated inhibition of carcinogenesis by mechanistic modulation of deregulated signaling pathways has revolutionized the field of translational oncology. Lycium barbarum has antioxidant and anticarcinogenic effects. The antioxidant activity of the extract and its effect on Ehrlich ascites tumor (EAT) were investigated using in vivo and in vitro techniques. EAT cells were injected into Balb/C mice to create stock mice. EAT cells withdrawn from stock mice were used in equal volumes in the studies. The in vivo study consisted of control and treatment groups (200 mg/kg fractions above and below 50 kDa of extracts). The liver tissues were evaluated for histopathological (H&E), DNA damage (Comet assay), and proliferation (AgNOR staining) status. The in vitro study consisted of control and treatment groups (1500 and 2000 µg/ml of extracts). Cell viability and apoptosis were evaluated. As a result, a decrease in the adhesion of EAT cells, and decreased DNA damage were observed in mice intraperitoneally administered with the fractions of Lycium barbarum. The extracts both below and above 50 kDa increased apoptotic death in cancer cells. The extract above 50 kDa was more active than those below 50 kDa. Lycium barbarum consumption may be effectual in preventing cancer formation and slowing the progression of cancer.

MiRNA-targeting oligonucleotide constructs with various mechanisms of action as effective inhibitors of carcinogenesis

INTRODUCTION. The development of malignant neoplasms is associated with changes in the expression of small non-coding RNAs (miRNAs). This emphasises the need for research into the development of miRNA-targeted inhibitors as a promising approach to cancer treatment.AIM. This study aimed to compare current strategies for suppressing the functional activity of tumour-associated miRNAs based on the use of therapeutic nucleic acids and to determine the application potential of these strategies.DISCUSSION. This study analysed known oligonucleotide-based miRNA inhibitors with different mechanisms of action. Based on their mechanism of action, miRNA-targeted inhibitors can be classified into two groups. The first group of miRNA-targeted inhibitors exhibits an indirect inhibitory effect, either by blocking functional connections between miRNAs and specific mRNA targets through the use of miRNA-masking oligonucleotides or by introducing mutations into miRNA genes and disrupting gene biosynthesis processes through the use of the CRISPR/Cas system. Despite their relatively high biological potential, these strategies are mostly used as search tools to study miRNA functional roles and molecular interactions in carcinogenesis. The second group of oligonucleotide constructs interacts with miRNA targets directly, which leads to steric blocking or degradation of oncogenic microRNAs. These miRNA-binding oligonucleotide constructs come in a variety of structural variants, including miRNA sponges, RNA zippers, antisense oligonucleotides, and miRNases, which demonstrate high therapeutic potential in vitro and in vivo.CONCLUSION. The described analysis of the biological properties, therapeutic potential, and key advantages of the developed miRNA-targeted oligonucleotide constructs helps outline the areas for their potential practical application in cancer treatment.

Role of melatonin in carcinogenesis and metastasis: From mechanistic insights to intermeshed networks of noncoding RNAs.

In recent years, seminal studies have been devoted to unraveling the puzzling mysteries associated with the cancer preventive/inhibitory role of melatonin. Our current knowledge of the translational mechanisms and the detailed structural insights have highlighted the characteristically exclusive role of melatonin in the inhibition of carcinogenesis and metastatic dissemination. This mini-review outlines recent discoveries related to mechanistic role of melatonin in prevention of carcinogenesis and metastasis. Moreover, another exciting facet of this mini-review is related to phenomenal breakthroughs linked with regulation of noncoding RNAs by melatonin in wide variety of cancers.

Role of kiwifruit in the inhibition of carcinogenesis: Proof-of-concept from cell culture studies and xenografted mice

Abstract Kiwifruit initially gained the limelight because of its remarkable health benefits. Still, its mechanistic involvement in the chemoprevention of carcinogenesis and metastasis has enabled researchers to evaluate anticancer and anti-metastatic effects in cell culture studies and xenografted mice. Interdisciplinary researchers have witnessed groundbreaking discoveries related to the pharmacological targeting of oncogenic proteins by kiwifruit in xenografted mice. Therefore, kiwifruit extracts, bioactive molecules, and nanovesicles have been investigated in different cancers. Although its importance was previously unrecognized, kiwifruit-derived nanovesicles are expected to showcase an increasingly prominent role in the chemoprevention of cancer as strategically preferable delivery vehicles. Accumulating evidence has started unraveling pleiotropic regulation of protein networks and biochemical modifications by kiwifruit in various cancers. Ubiquitination, autophagy, and mitophagy are some of the critical pathways reported to be regulated by kiwifruit extracts and bioactive chemicals. Nevertheless, realistically, this is the beginning of a new era in the context of mechanistic regulation of a myriad of cell signaling cascades in the prevention of carcinogenesis and metastasis.

Black Pepper’s Anti-Aging and Chemo-preventive Properties: A Review

The possible uses of black pepper, a common spice used for cooking, have been expanded. Despite countless studies on its advantageous biological effects, it would be difficult to determine its effectiveness as an anti-aging and chemo-preventive medication. Piperine, chavicine, caryophyllene, and sabinene are a few examples of black pepper components that exhibit pharmacological characteristics. This article reviews black pepper's main ingredients and discusses how effective it is at preventing aging and cancer. Using Google Scholar, PubMed, and Medline for our electronic research, we screened pertinent papers from scientific journals. To help with the explanation in the narrative, all the data was compiled and summarized into tables and graphs. Overall, the anti-aging properties of black pepper and its constituents are exhibited through several pathways, including senescence prevention, antioxidant protection, control of ROS levels, and the inhibition of aging-related enzymes. Additionally, cell cycle regulation, antiangiogenic and anti-metastatic action, apoptosis induction, and the suppression of carcinogenesis are some of the mechanisms utilized in cancer prevention activities. It has been shown to have synergistic effects on several cancer cells when combined with doxorubicin. According to these studies, black pepper could be considered for development as an anti-aging and chemo-preventive agent.

AGAP2-AS1 promotes the assembly of m6A methyltransferases and activation of the IL6/STAT3 pathway by binding with WTAP in the carcinogenesis of gastric cancer.

Owing to the lack of biomarkers for early diagnosis, gastric cancer (GC) is often associated with a poor prognosis. Thus, there is an urgent need to identify early molecular targets in GC. Dysregulated long noncoding RNAs (lncRNAs) have been evaluated by integrated bioinformatics analysis; and we investigate their specific role and potential mechanism via N6-methyladenosine (m6A) methylation modification in the carcinogenesis and progression of GC. In this study, we report upregulation of lncRNA AGAP2-AS1, activated by a gain of H3K4Me3, in GC tissues and cells. AGAP2-AS1 was linked to adverse prognosis in patients with GC. Functionally, AGAP2-AS1 knockdown inhibited cell proliferation and migration of GC cells. Mechanistically, AGAP2-AS1 bound WT1-associated protein (WTAP) to promote the formation of the WTAP/methyltransferase-like 3 (METTL3)/METTL14 m6A methyltransferase complex. AGAP2-AS1 stabilized signal transducer and activator of transcription 3 (STAT3) mRNA in an m6A-dependent manner and, thus, activated the interleukin 6 (IL6)/STAT3 pathway. Importantly, activation of the AGAP2-AS1/WTAP/STAT3 pathways promoted cell proliferation and migration in GC. Collectively, the present findings revealed a novel regulatory relationship between lncRNA and m6A modification. Furthermore, targeting the AGAP2-AS1/WTAP/STAT3 axis may be a promising strategy for the inhibition of inflammation-mediated carcinogenesis and progression in GC.

Phytochemistry, antioxidant, anticancer, and acute toxicity of traditional medicinal food Biarum bovei (Kardeh)

BackgroundThe Biarum species (Kardeh) has been consumed as a traditional functional food and medicine for decades. The current study investigates the phytochemistry, in-vitro and in-vivo bioactivities of methanol extracts of B. bovei.MethodsThe Gas-chromatography mass spectrophotometer (GS/GS-MS) was used to analyze the phytochemical profile of the methanol extracts of B. bovei leaves and corms. The B. bovei extracts (BBE) were also investigated for in-vitro antioxidant, anticancer, and in-vivo acute toxicity (2000 mg/kg) activities.ResultsThe chemical profiling of BBE revealed mainly fatty acids, phytosterol, alcohols, and hydrocarbon compounds. Namely, Linoleic acid, eliadic acid, palmitic acid, 22,23-dihydro-stigmasterol, and campesterol. The antioxidant activity of BBE ranged between 0.24–3.85 μg TE/mL based on different assays. The extracts also exhibited significant anticancer activity against DU-145 (prostate cancer cells), MCF-7 (human breast adenocarcinoma), and HeLa (human cervical cancer) cell lines with IC50 values ranging between 22.73–44.24 μg/mL. Rats fed on 2000 mg/kg dosage of BBE showed absence of any toxicological sign or serum biochemical changes.ConclusionThe detected phytochemicals and bioactivities of BBE scientifically backup the folkloric usage as an important source of nutraceuticals and alternative medicine for oxidative stress-related diseases and carcinogenesis inhibition.

Review of Small Molecule Anticancer NF-κB Inhibitors

Cancer is one of the most common diseases in the world. Th e transcription factor NF-κB plays a key role in various physiological processes including immune response, cell proliferation, cell apoptosis and inflammation. Due to participation of NF-kappa B signaling pathways in carcinogenesis, angiogenesis, and tumor resistance to chemo- and radiotherapy, the factor is considered to be the ideal target for pharmacological treatment of cancer. Th e paper presents a literature review of the RSCI, PubMed, Scopus, Web of Science, Chemical Abstracts NCCN databases and other open access data. The carcinogenesis inhibitors were selected from all NF-κB inhibitors found. Inhibitors with antitumor activity of analytical interest include Bruton tyrosine kinase (BTK) inhibitors, cellular inhibitors of apoptosis proteins (c-IAP), proteasome inhibitors, and one inhibitor of NF-κB translocation to the nucleus. Th e authors analyzed products of diff erent development stages with recorded antitumor activity to varying degrees. NF-κB inhibitors are promising drug candidates, but since NF-κB is involved in most biological processes and the broad spectrum of action can cause side eff ects, the selective action of these compounds is to be explored.

Plasmon-enhanced fluorescence for ellagic acid detection based on surface structure of gold nanoparticles.

Ellagic acid (EA), as a natural polyphenolic acid, is considered a naturally occurring inhibitor of carcinogenesis. Herein, we developed a plasmon-enhanced fluorescence (PEF) probe for EA detection based on silica-coated gold nanoparticles (Au NPs). A silica shell was designed to control the distance between silica quantum dots (Si QDs) and Au NPs. The experimental results indicated that an 8.8-fold fluorescence enhancement was obtained compared with the original Si QDs. Three-dimensional finite-difference time-domain (3D-FDTD) simulations further demonstrated that the local electric field enhancement around Au NPs led to the fluorescence enhancement. In addition, the fluorescent sensor was applied for the sensitive detection of EA with a detection limit of 0.14μM. It can be used to detect EA in pomegranate rind with a recovery rate of 100.26-107.93%. It can also be applied to the analysis of other substances by changing the identification substances. These experimental results indicated that the probe provides a good option for clinical analysis and food safety.

Molecular mechanisms underlying the epigallocatechin-3-gallate-mediated inhibition of oral squamous cell carcinogenesis

ObjectivesTo reveal the mechanisms underlying the epigallocatechin-3-gallate (EGCG)-mediated inhibition of carcinogenesis and the related regulatory signaling pathways. DesignThe effect of EGCG on the proliferation of OSCC cells was examined. SuperPred, ChEMBL, Swiss TargetPrediction, DisGeNET, GeneCards, and National Center for Biotechnology Information databases were used to predict the EGCG target genes and oral leukoplakia (OL)-related, oral submucosal fibrosis (OSF)-related, and OSCC-related genes. The binding of EGCG to the target proteins was simulated using AutoDock and PyMOL. The Cancer Genome Atlas (TCGA) dataset was subjected to consensus clustering analysis to predict the downstream molecules associated with these targets, as well as their potential functions and pathways. ResultsEGCG significantly inhibited OSCC cell proliferation (p < 0.001). By comparing EGCG target genes with genes linked to oral potentially malignant disorder (OPMD) and OSCC, a total of eleven potential EGCG target genes were identified. Furthermore, EGCG has the capacity to bind to eleven proteins. Based on consensus clustering and enrichment analysis, it is suggested that EGCG may hinder the progression of cancer by altering the cell cycle and invasive properties in precancerous lesions of the oral cavity. Some possible strategies for modifying the cell cycle and invasive properties may include EGCG-mediated suppression of specific genes and proteins, which are associated with cancer development. ConclusionsThis study investigated the molecular mechanisms and signaling pathways associated with the EGCG-induced suppression of OSCC. The identification of specific pharmacological targets of EGCG during carcinogenesis is crucial for the development of innovative combination therapies involving EGCG.

Furanocoumarin Notopterol: Inhibition of Hepatocellular Carcinogenesis through Suppression of Cancer Stemness Signaling and Induction of Oxidative Stress-Associated Cell Death.

Hepatocellular carcinoma (HCC) remains an aggressive malignancy with a poor prognosis and a leading cause of cancer-related mortality globally. Cumulative evidence suggests critical roles for endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in chronic liver diseases. However, the role of ER stress in HCC pathogenesis, aggressiveness and therapy response remains unclear and understudied. Against this background, the present study evaluated the therapeutic efficacy and feasibility of notopterol (NOT), a furanocoumarin and principal component of Notopterygium incisum, in the modulation of ER stress and cancer stemness, and the subsequent effect on liver oncogenicity. An array of biomolecular methods including Western blot, drug cytotoxicity, cell motility, immunofluorescence, colony and tumorsphere formation, flow-cytometric mitochondrial function, GSH/GSSG ratio, and tumor xenograft ex vivo assays were used in the study. Herein, we demonstrated that NOT significantly suppresses the viability, migration, and invasion capacity of the human HCC HepJ5 and Mahlavu cell lines by disrupting ATF4 expression, inhibiting JAK2 activation, and downregulating the GPX1 and SOD1 expression in vitro. NOT also markedly suppressed the expression of vimentin (VIM), snail, b-catenin, and N-cadherin in the HCC cells, dose-dependently. Treatment with NOT significantly attenuated cancer stem cells (CSCs)-like phenotypes, namely colony and tumorsphere formation, with the concomitant downregulation of stemness markers OCT4, SOX2, CD133, and upregulated PARP-1 cleavage, dose-dependently. We also demonstrated that NOT anticancer activity was strongly associated with increased cellular reactive oxidative stress (ROS) but, conversely, reduced mitochondrial membrane potential and function in the HepJ5 and Mahlavu cells in vitro. Our tumor xenograft studies showed that compared with sorafenib, NOT elicited greater tumor growth suppression without adverse changes in mice body weights. Compared with the untreated control and sorafenib-treated mice, NOT-treated mice exhibited markedly greater apoptosis ex vivo, and this was associated with the co-suppression of stemness and drug-resistance markers OCT4, SOX2, ALDH1, and the upregulation of endoplasmic reticulum stress and oxidative stress factors PERK and CHOP. In summary, we demonstrated for the first time that NOT exhibits strong anticancer activity via the suppression of cancer stemness, enhanced endoplasmic reticulum stress and increased oxidative stress thus projecting NOT as a potentially effective therapeutic agent against HCC.

Integrated Microbiota and Metabolite Changes following Rice Bran Intake during Murine Inflammatory Colitis-Associated Colon Cancer and in Colorectal Cancer Survivors.

Dietary rice bran-mediated inhibition of colon carcinogenesis was demonstrated previously for carcinogen-induced rodent models via multiple anti-cancer mechanisms. This study investigated the role of dietary rice bran-mediated changes to fecal microbiota and metabolites over the time course of colon carcinogenesis and compared murine fecal metabolites to human stool metabolic profiles following rice bran consumption by colorectal cancer survivors (NCT01929122). Forty adult male BALB/c mice were subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colon carcinogenesis and randomized to control AIN93M (n = 20) or diets containing 10% w/w heat-stabilized rice bran (n = 20). Feces were serially collected for 16S rRNA amplicon sequencing and non-targeted metabolomics. Fecal microbiota richness and diversity was increased in mice and humans with dietary rice bran treatment. Key drivers of differential bacterial abundances from rice bran intake in mice included Akkermansia, Lactococcus, Lachnospiraceae, and Eubacterium xylanophilum. Murine fecal metabolomics revealed 592 biochemical identities with notable changes to fatty acids, phenolics, and vitamins. Monoacylglycerols, dihydroferulate, 2-hydroxyhippurate (salicylurate), ferulic acid 4-sulfate, and vitamin B6 and E isomers significantly differed between rice bran- and control-fed mice. The kinetics of murine metabolic changes by the host and gut microbiome following rice bran consumption complemented changes observed in humans for apigenin, N-acetylhistamine, and ethylmalonate in feces. Increased enterolactone abundance is a novel diet-driven microbial metabolite fecal biomarker following rice bran consumption in mice and humans from this study. Dietary rice bran bioactivity via gut microbiome metabolism in mice and humans contributes to protection against colorectal cancer. The findings from this study provide compelling support for rice bran in clinical and public health guidelines for colorectal cancer prevention and control.

Bufalin-Mediated Regulation of Cell Signaling Pathways in Different Cancers: Spotlight on JAK/STAT, Wnt/β-Catenin, mTOR, TRAIL/TRAIL-R, and Non-Coding RNAs

The renaissance of research into natural products has unequivocally and paradigmatically shifted our knowledge about the significant role of natural products in cancer chemoprevention. Bufalin is a pharmacologically active molecule isolated from the skin of the toad Bufo gargarizans or Bufo melanostictus. Bufalin has characteristically unique properties to regulate multiple molecular targets and can be used to harness multi-targeted therapeutic regimes against different cancers. There is burgeoning evidence related to functional roles of signaling cascades in carcinogenesis and metastasis. Bufalin has been reported to regulate pleiotropically a myriad of signal transduction cascades in various cancers. Importantly, bufalin mechanistically regulated JAK/STAT, Wnt/β-Catenin, mTOR, TRAIL/TRAIL-R, EGFR, and c-MET pathways. Furthermore, bufalin-mediated modulation of non-coding RNAs in different cancers has also started to gain tremendous momentum. Similarly, bufalin-mediated targeting of tumor microenvironments and tumor macrophages is an area of exciting research and we have only started to scratch the surface of the complicated nature of molecular oncology. Cell culture studies and animal models provide proof-of-concept for the impetus role of bufalin in the inhibition of carcinogenesis and metastasis. Bufalin-related clinical studies are insufficient and interdisciplinary researchers require detailed analysis of the existing knowledge gaps.

Dry Beans Inhibit Azoxymethane-Induced Colon Carcinogenesis in F344 Rats

Epidemiological studies show a low incidence of colon cancer in many Latin American countries where the consumption of dry beans (e.g., pinto) is high. The purpose of this study was to use rats as an animal model to obtain experimental data on the inhibition of colon carcinogenesis by dry beans. Fifty-three 5-wk-old weanling male F344 rats were randomly assigned by weight to the following groups: control (11 rats), casein diet (21 rats), and bean diet (21 rats). Animals fed the casein and bean diets were treated with the carcinogen azoxymethane (AOM) once weekly for 2 wk. Rats in the control group also consumed the casein diet but were not exposed to AOM. All diets were isocaloric. The protein concentration of the diets was adjusted to 18 g/100 g with casein, and the fat concentration was adjusted to 5 g/100 g with corn oil. Rats fed the bean diet had significantly fewer colon adenocarcinomas (P< 0.05) than rats fed the casein diet (5 vs. 22 tumors), and significantly fewer rats fed the bean diet (P< 0.05) had colonic tumors than did casein-fed rats (24 vs. 50%). Tumor multiplicity was also significantly lower for the bean-fed rats, and significantly fewer (P< 0.05) tumors per tumor-bearing rat were observed in bean-fed rats than in casein-fed rats (1.0 ± 0.0 vs. 2.5 ± 0.6). This study demonstrates that dry beans contain anticarcinogenic compounds capable of inhibiting AOM-induced colon cancer in rats. However, the specific anticarcinogenic components within dry beans have not been identified, and it is unclear whether dietary fiber, phytochemicals or other components within dry beans are primarily responsible for the anticarcinogenic properties of beans.

High-value biological compounds in jackfruit (Artocarpus heterophyllus Lam.) and their relationship with carcinogenesis

Jackfruit contains high-value biological compounds (HVBC) with important biological activity in the inhibition of carcinogenesis, through various mechanisms. This study aimed to identify the HVBC in a methanolic fraction of an extract of jackfruit; which was reported with antimutagenic and antiproliferative activity against PC3 cells (prostate cancer). The profile includes 3 organic acids, 5 phenolic acids, 12 flavonoids, and 2 carotenoids. The identification permitted the establishment of postulates about the possible inhibition mechanisms of the compounds reported with greater biological activity in the different phases of the carcinogenesis process, such as apigenin, artocarpin, cuadraflavone C, moracin C, and β-carotene.

Exploring structural effects in a new class of NRF2 inhibitors.

NRF2 is a transcription factor that controls the cellular response to various stressors, such as reactive oxygen and nitrogen species. As such, it plays a key role in the suppression of carcinogenesis, but constitutive NRF2 expression in cancer cells leads to resistance to chemotherapeutics and promotes metastasis. As a result, inhibition of the NRF2 pathway is a target for new drugs, especially for use in conjunction with established chemotherapeutic agents like carboplatin and 5-fluorouracil. A new class of NRF2 inhibitors has been discovered with substituted nicotinonitriles, such as MSU38225. In this work, the effects on NRF2 inhibition with structural changes were explored. Through these studies, we identified a few compounds with as good or better activity than the initial hit but with greatly improved solubility. The syntheses involved a variety of metal-catalyzed reactions, including titanium multicomponent coupling reactions and various Pd and Cu coupling reactions. In addition to inhibiting NRF2 activity, these new compounds inhibited the proliferation and migration of lung cancer cells in which the NRF2 pathway is constitutively activated.

Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis.

The pursual of novel anticancer molecules from natural sources has gained worthwhile appreciation, and a significant fraction of conceptual knowledge has revolutionized our understanding about heterogeneous nature of cancer. Betulinic acid has fascinated interdisciplinary researchers due to its tremendous pharmacological properties. Ground-breaking discoveries have unraveled previously unprecedented empirical proof-of-concept about momentous chemopreventive role of betulinic acid against carcinogenesis and metastasis. Deregulation of cell signaling pathways has been reported to play a linchpin role in cancer progression and colonization of metastatically competent cancer cells to the distant organs for the development of secondary tumors. Importantly, betulinic acid has demonstrated unique properties to mechanistically modulate oncogenic transduction cascades. In this mini-review, we have attempted to provide a sophisticated compendium of regulatory role of betulinic acid in cancer chemoprevention. We have partitioned this multi-component review into different sections in which we summarized landmark research-works which highlighted betulinic acid mediated regulation of JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and ubiquitination pathways in the inhibition of cancer. In parallel, betulinic acid mediated regulation of signaling cascades and non-coding RNAs will be critically analyzed in cell culture and animal model studies. Better comprehension of the pharmaceutical features of betulinic acid and mapping of the existing knowledge gaps will be valuable in the translatability of preclinical studies into rationally designed clinical trials.

In vitro and in silico perspectives to explain anticancer activity of a novel syringic acid analog ((4-(1H-1, 3-benzodiazol-2-yl)-2, 6-dimethoxy phenol)) through apoptosis activation and NFkB inhibition in K562 leukemia cells

Syringic acid (SA) is an active carcinogenesis inhibitor; however, the low bioavailability and unstable functional groups hinder its activity. Here, a chemically synthesized novel SA analog (SA10) is evaluated for its anticancer activity using in-vitro and in-silico studies. K562 cell line study revealed that SA10 had shown a higher rate of inhibition (IC50 = 50.40 μg/mL) than its parental compound, SA (IC50 = 96.92 μg/mL), at 50 μM concentration. The inhibition ratio was also been evaluated by checking the expression level of NFkB and Bcl-2 and showing that SA10 has two-fold increase in the inhibitory mechanism than SA. This result demonstrates that SA10 acts as an NFkB inhibitor and an apoptosis inducer. Further, molecular docking and simulation have been performed to get insights into the possible inhibitory mechanism of SA and SA10 on NFkB at the atomistic level. The molecular docking results exemplify that both SA and SA10 bind to the active site of NFkB, thereby interfering with the association between DNA and NFkB. SA10 exhibits a more robust binding affinity than SA and is firmly docked well into the interior of the NFkB, as confirmed by MM-PBSA calculations. In a nutshell, the Benzimidazole scaffold containing SA10 has shown more NFkB inhibitory activity in K562 cells than SA, which could be helpful as an ideal therapeutic NFkB inhibitor for treating cancers.

The dual role and mutual dependence of heme/HO-1/Bach1 axis in the carcinogenic and anti-carcinogenic intersection.

In physiological concentrations, heme is nontoxic to the cell and is essential for cell survival and proliferation. Increasing intracellular heme concentrations beyond normal levels, however, will lead to carcinogenesis and facilitate the survival of tumor cells. Simultaneously, heme in an abnormally high quantity is also a potent inducer of tumor cell death, contributing to its ability to generate oxidative stress on the cells by boosting oxidative phosphorylation and suppressing tumors through ferroptosis. During tumorigenesis and progression, therefore, heme works as a double-edged sword. Heme oxygenase 1 (HO-1) is the rate-limiting enzyme in heme catabolism, which converts heme into physiologically active catabolites of carbon monoxide (CO), biliverdin, and ferrous iron (Fe2+). HO-1 maintains redox equilibrium in healthy cells and functions as a carcinogenesis inhibitor. It is widely recognized that HO-1 is involved in the adaptive response to cellular stress and the anti-inflammation effect. Notably, its expression level in cancer cells corresponds with tumor growth, aggressiveness, metastasis, and angiogenesis. Besides, heme-binding transcription factor BTB and CNC homology 1 (Bach1) play a critical regulatory role in heme homeostasis, oxidative stress and senescence, cell cycle, angiogenesis, immune cell differentiation, and autoimmune disorders. Moreover, it was found that Bach1 influences cancer cells' metabolism and metastatic capacity. Bach1 controls heme level by adjusting HO-1 expression, establishing a negative feedback loop. Herein, the authors review recent studies on heme, HO-1, and Bach1 in cancer. Specifically, they cover the following areas: (1) the carcinogenic and anticarcinogenic aspects of heme; (2) the carcinogenic and anticarcinogenic aspects of HO-1; (3) the carcinogenic and anticarcinogenic aspects of Bach1; (4) the interactions of the heme/HO-1/Bach1 axis involved in tumor progression. This review summarized the literature about the dual role of the heme/HO-1/Bach1 axis and their mutual dependence in the carcinogenesis and anti-carcinogenesis intersection.

Lactobacillus Species as Probiotics: Isolation Sources and Health Benefits

Recently, the attention to exploring and applying probiotics has been increased. Probiotics are living microscopic organisms that have valuable impacts on health when consumed in adequate amounts. One of the most popular widespread utilized probiotics for many years until now is the Lactobacillus species which exemplifies the hugest heterogeneous group among the lactic acid bacteria (LAB) that normally occupy many environments that contain high nutrient levels such as soil, humans, waters, plants, animals and even air without causing any illness. The purpose of this work is to review and demonstrate the wide diversity of lactobacilli isolation sources and related health benefits applications of the strains discovered in order to break the familiar sources of lactobacillus spp., thereby encouraging more research into unconventional sources and opening up opportunities for clinical applications of Lactobacillus spp. As a result, the isolation sources of lactobacillus spp. in this review have been split into two groups based on the environmental condition, including fermented and non-fermented habitats described as lactobacilli probiotic sources. The unique Lactobacilli isolated from various sources are regarded as potential therapies for a variety of illnesses and physiological abnormalities, including immunomodulation, suppression of carcinogenesis, and cholesterol reduction, in addition to their capacity to guard against infections. This will be highly significant for revealing updated information about Lactobacillus spp. that has attracted considerable attention due to its potential application in clinical practices.