Anticarcinogenic Effects Research Articles

Recent Developments in Luteolin-Loaded Nanoformulations for Enhanced Anti-Carcinogenic Activities: Insights from In Vitro and In Vivo Studies

With approximately 18 million people affected by cancer in 2020 globally, scientists are exploring innovative approaches to develop effective treatments for various types of cancer. Traditional chemotherapy drugs, although effective against cancer cells, often lead to significant side effects on healthy tissues, such as hair loss, anemia, and nausea. To discover safer alternatives, researchers are investigating natural bioactive compounds found abundantly in plants. Luteolin, a flavonoid found in celery and artichokes, stands out due to its diverse anti-carcinogenic properties, including inhibiting proliferation, inducing apoptosis, activating autophagy, and inhibiting angiogenesis and metastasis. However, the therapeutic potential of luteolin is hindered by challenges related to its bioavailability and solubility. This critical review explores the specific anti-carcinogenic properties of luteolin while analyzing the impact of its limited bioavailability and solubility on effectiveness. Additionally, it investigates the outcomes of encapsulating luteolin in nanoformulations, providing insights into potential strategies for enhancing its anti-carcinogenic effects. Finally, the review compares the efficacy of luteolin with and without nanoformulations. This review provides valuable insights into the potential of utilizing luteolin-loaded nanoformulations as a safer and more effective method for treating cancer, contributing to the ongoing efforts in improving cancer care and outcomes worldwide.

Targeted breast cancer therapy using novel nanovesicle formulations of Olea europaea extract

Olive leaf is a byproduct of the olive tree that is rich in phenolic compounds with potential anticarcinogenic effects against various cancers, including breast cancer. Nevertheless, the ingestion or topical application of such plant extracts faces certain limitations. These limitations can be addressed by encapsulating the extracts in nanovesicles to enhance their release and bioavailability. This study aims to develop nanovesicles using Olea europaea leaf extract to exploit its potential anti-cancer properties. Soy lecithin was used to form liposomes for encapsulation of the olive leaf extract. In addition, ethanol and glycerol were added to form ethosomes and glycerosomes, respectively. The antiproliferative effect of both the free extract and the three formed nanovesicles was tested in MCF7 and MCF10A cell lines. To comprehend the mechanisms leading to reduced cell viability after exposure to olive leaf extract and its nanovesicles, levels of reactive oxygen species (ROS), mitochondrial membrane potential, and apoptotic stage were evaluated. The results suggest that both, the nanovesicles and the free extract, are antiproliferative agents against MCF7 tumour cells. However, when examining the impact of olive leaf extract and the formulated nanovesicles on MCF10A cells, no reduction in cell viability was observed. Our findings indicate that the anti-tumour effect of the extract and its nanovesicles may be due to increased oxidative stress, mediated by mitochondrial damage. The mechanism through which olive leaf extract exerts its antiproliferative effect on the breast cancer tumour line implies that apoptosis may be induced by the extract via the involvement of a mitochondria-dependent ROS-mediated pathway.

The phytochemical composition of Kuzbass medicinal plants studied by spectrophotometry and chromatography

Flavonoids are plant polyphenols that exhibit biological activity with antibacterial, antiviral, antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic effects. The medicinal plants of Kuzbass have high contents of flavonoids and other polyphenolic compounds. Therefore, they can be used in medicinal preparations to prevent or treat serious diseases. We studied the following plants collected in Kuzbass: common thyme (Thymus vulgaris Linn., leaves and stems), woolly burdock (Arctium tomentosum Mill., roots), alfalfa (Medicago sativa L., leaves and stems), common lungwort (Pulmonaria officinalis L., leaves and stems), common yarrow (Achillea millefolium L., leaves and stems), red clover (Trifolium pratense L., leaves and stems), common ginseng (Panax ginseng, roots), sweetvetch (Hedysarum neglectum Ledeb., roots), and cow parsnip (Heracleum sibiricum L., inflorescences, leaves, and stems). To extract flavonoids, we used ethanol at concentrations of 40, 55, 60, 70, and 75%. Spectrophotometry was used to determine total flavonoids, while high-performance liquid chromatography was employed to study the qualitative and quantitative composition of the extracts. The highest yield of flavonoids was found in H. sibiricum leaves (at all concentrations except 70%), followed by the 55% and 70% ethanol extracts of T. vulgaris leaves and stems, as well as the 75% ethanol extract of A. millefolium leaves and stems. Thus, these plants have the greatest potential in being used in medicines. High-performance liquid chromatography showed the highest contents of polyphenolic compounds in the samples of P. officinalis, A. millefolium, T. vulgaris, and T. pratense. Our results can be used in further research to produce new medicinal preparations based on the medicinal plants of Kuzbass.

Double-Edged Sword Effect of Diet and Nutrition on Carcinogenic Molecular Pathways in Breast Cancer.

Environmental exposure to a mixture of chemical xenobiotics acts as a double-edged sword, promoting or suppressing tumorigenesis and the development of breast cancer (BC). Before anything else, we are what we eat. In this review, we highlight both "the good" and "the bad" sides of the daily human diet and dietary patterns that could influence BC risk (BCR) and incidence. Thus, regularly eating new, diversified, colorful, clean, nutrient-rich, energy-boosting, and raw food, increases apoptosis and autophagy, antioxidation, cell cycle arrest, anti-inflammation, and the immune response against BC cells. Moreover, a healthy diet could lead to a reduction in or the inhibition of genomic instability, BC cell stemness, growth, proliferation, invasion, migration, and distant metastasis. We also emphasize that, in addition to beneficial compounds, our food is more and more contaminated by chemicals with harmful effects, which interact with each other and with endogenous proteins and lipids, resulting in synergistic or antagonistic effects. Thus, a healthy and diverse diet, combined with appropriate nutritional behaviors, can exert anti-carcinogenic effects and improve treatment efficacy, BC patient outcomes, and the overall quality of life of BC patients.

Effect of silibinin on GAS6/sAXL and JAK/STAT pathways in human cholangiocarcinoma cell line

Abstract Objectives Cholangiocarcinoma (CCA) is a highly heterogeneous biliary malignant tumor. Studies have demonstrated that JAK/STAT signaling is activated in many types of cancer. In addition, JAK/STAT is activated downstream of AXL, and the AXL receptor is activated by its ligand, GAS6. In this study, we investigated the anticarcinogenic effect of silibinin and its relationship with the GAS6/AXL ve JAK/STAT pathway in the human EGI-1 cell line. Methods Cell viability, apoptosis, and cell cycle were measured by Muse Cell Analyzer. All the protein levels were determined by the ELISA method. Results We observed that silibinin significantly reduced cell proliferation and colony formation (p<0.05, p<0.001, respectively). Silibinin also significantly induced total apoptosis and the G0/G1 phase of the cell cycle (p<0.01). We observed that silibinin significantly decreased JAK2 levels while increased STAT1 levels compared to the controls respectively (p<0.001; p<0.001). Besides, silibinin statistically decreased the levels of sAXL; however, numerically, but not statistically, it increased the level of GAS6 (p>0.05). Conclusions Silibinin reduces colony formation, inducing apoptosis and arresting cancer cells in the G0/G1 phase, which is an indicator of its anticancer activity. In addition, silibinin decreased the levels of JAK2 and sAXL, which contributes to the development of cancer, and increased the levels of STAT1, suggesting silibinin’s antiproliferative effects.

Exploring the Anti-Carcinogenic Effect of Choline in Limiting the Progression of Breast Cancer in Females

Background: Breast cancer is one of the most common cancers among females worldwide, influenced by genetic, environmental, and dietary factors. Choline, an essential nutrient, plays a crucial role in cell membrane integrity and DNA methylation, which are significant for maintaining genomic stability.Objective: This review aims to explore the anti-carcinogenic effects of choline in limiting the progression of breast cancer.Methods: A narrative review was conducted using electronic databases, including PubMed, Google Scholar, and ScienceDirect, to identify relevant studies. Data were extracted from observational studies, clinical trials, and meta-analyses that focused on choline intake and breast cancer risk. Studies were appraised using established quality assessment tools.Results: Evidence suggests that adequate choline intake is linked to reduced breast cancer risk through its role in DNA methylation and gene regulation. However, findings are inconsistent due to genetic variations and methodological differences.Conclusion: While choline shows potential as a protective nutrient, further research is needed to clarify its role in breast cancer prevention, considering genetic and dietary variations

The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women with In Situ or Early-Stage Invasive Breast Cancer.

Statins, inhibitors of HMG-CoA reductase, have been shown to have potential anti-carcinogenic effects through the inhibition of the mevalonate pathway and their impact on Ras and RhoGTAases. Prior studies have demonstrated a reduction in breast tumor proliferation, as well as increased apoptosis, among women with early-stage breast cancer who received statins between the time of diagnosis and the time of surgery. The aim of this study was to evaluate the impact of short-term oral high-potency statin therapy on the expression of markers of breast tumor proliferation, apoptosis, and cell cycle arrest in a window-of-opportunity trial. This single-arm study enrolled 24 women with stage 0-II invasive breast cancer who were administered daily simvastatin (20 mg) for 2-4 weeks between diagnosis and surgical resection. Pre- and post-treatment tumor samples were analyzed for fold changes in Ki-67, cyclin D1, p27, and cleaved caspase-3 (CC3) expression. Out of 24 enrolled participants, 18 received statin treatment and 17 were evaluable for changes in marker expression. There was no significant change in Ki-67 expression (fold change = 1.4, p = 0.597). There were, however, significant increases in the expression of cyclin D1 (fold change = 2.8, p = 0.0003), p27 cytoplasmic (fold change = 3.2, p = 0.025), and CC3 (fold change = 2.1, p = 0.016). Statin treatment was well tolerated, with two reported grade-1 adverse events. These results align with previous window-of-opportunity studies suggesting a pro-apoptotic role of statins in breast cancer. The increased expression of markers of cell cycle arrest and apoptosis seen in this window-of-opportunity study supports further investigation into the anti-cancer properties of statins in larger-scale clinical trials.

Roles of intralesional bacteria in the initiation and progression of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the predominant form of head and neck cancer, often diagnosed at late stages, resulting in a poor prognosis. Recent studies indicate a potential association between OSCC and microbial presence. Microorganisms have been identified in various tumors and lesions, including OSCC and oral potentially malignant disorders (OPMDs). Intralesional microbiota are considered important components of the tumor microenvironment (TME) and may contribute to carcinogenesis. Sources were collected through thorough searches of databases PubMed and Embase. The review focused on microbial characteristics, potential origins, and their impact on cancer progression. Bacteria display varying abundance and diversity throughout the stages of OSCC and OPMDs. Intraleisional bacteria may have diverse sources, including not only oral plaque and saliva but also potentially the gut. Intralesional bacteria have both pro-carcinogenic and anti-carcinogenic effects, affecting processes like cell proliferation, invasion, and immune response. Intralesional microbiota are crucial in OSCC and OPMDs, influencing both disease progression and treatments. Despite their significance, challenges like inconsistent sampling and microbial identification remain. Future research is required to fully understand their role and improve clinical applications.

Endogenous osteoprotegerin (OPG) represses ERα and promotes stemness and chemoresistance in breast cancer cells

Breast cancer (BC) is the most prevalent cancer and the leading cause of death among women worldwide. The osteoprotegerin (OPG) cytokine, a decoy receptor for RANKL and a key player in bone homeostasis, has pro-and anti-carcinogenic effects in various types of cancer, including breast neoplasms. In the present study, we have shown that ectopic expression of OPG in breast epithelial/cancer cells promotes the pro-metastatic processes epithelial-to-mesenchymal transition (EMT), stemness, angiogenesis as well as the activation of breast stromal fibroblasts. Furthermore, proteomics analysis, which allows the identification and quantification of a plethora of known and unknown proteins, has shown a strong and significant correlation between OPG upregulation and the expression of proteins with functions in EMT and stemness. On the other hand, OPG knockdown in triple-negative breast cancer (TNBC) cells inhibited the formation of cancer stem cells. Importantly, while OPG upregulation significantly enhanced the resistance of luminal BC cells to cisplatin and docetaxel, OPG downregulation sensitized TNBC cells to these chemotherapeutic drugs. We have also shown that OPG negatively controls estrogen receptor α (ERα), and OPG upregulation correlated well with the expression of genes related to ER-negative claudin low cells. Collectively, these results show that OPG promotes stemness and the consequent chemoresistance of breast cancer cells.

The therapeutic potential and molecular mechanism of Alpha-pinene, Gamma-terpinene, and P-cymene against melanoma cells

The purpose of this study is to investigate the potential anticarcinogenic effects of three phytochemicals, namely Alpha-pinene (AP), Gamma-terpinene (GT), and P-cymene (PC), on melanoma cells (A2058 cell line). Additionally, the study aims to explore the synergistic activities of these phytochemicals with Dacarbazine, a chemotherapy drug. To understand the molecular mechanism involved in apoptosis induction in the A-2058 cell line, it was used AO/EB staining for apoptosis detection and cell cycle analysis, monitored through flow cytometry. It also determined the mRNA expression levels of different apoptosis-regulatory genes, including p53, Bax, NF-kB, Bcl-2, Bcl-xl, and caspase-3. The antitumor activities of these phytochemicals and their combinations were investigated in a subcutaneous mouse tumor model. The tumor diameter was 21.4 ± 1.1 mm in the Dacarbazine treatment group and 42.4 ± 3.1 mm in the control group. The antitumoral activities of AP and PC in the tumor model were similar to those of Dacarbazine. On the other hand, GT exhibited remarkable antitumoral activity, with a 1.75-fold reduction in tumor diameter compared to the Dacarbazine group. When different combinations of phytochemicals and Dacarbazine were used, the GT plus Dacarbazine treatment group was found to have a 3.5-fold reduction in tumor diameter compared to the Dacarbazine group. The tumor diameters in the Dacarbazine, AP plus GT, GT plus Dacarbazine, and AP plus Dacarbazine treatment groups were 21.4 ± 1.1, 7.6 ± 2.2, 8.6 ± 0.5, and 6.2 ± 1.9 mm, respectively.

Saikosaponin D potentiates the antineoplastic effects of doxorubicin in drug-resistant breast cancer through perturbing NQO1-mediated intracellular redox balance

BackgroundDrug resistance to doxorubicin (DOX) significantly limits its therapeutic efficacy in breast cancer (BC) patients. Saikosaponin D (SSD), a triterpene saponin derived from the traditional herb Radix Bupleuri, has shown promise as a chemotherapeutic sensitizer in preclinical studies due to its notable antitumor activity. However, the role and mechanism of SSD in DOX-resistant BC cells remain largely unexplored. PurposeThis study aimed to investigate the chemosensitizing effect of SSD on DOX-resistant BC and the underlying molecular mechanisms both in vitro and in vivo. MethodsIn vitro assays, including cell viability, clone formation, three-dimensional tumor spheroid growth, and apoptosis analysis, were conducted to evaluate the synergistic effect of SSD and DOX on resistant BC cells. Reactive oxygen species (ROS), GSH/GSSG, NADPH/NADP+, and NADH/NAD+ detections were employed to assess the impact of SSD on cellular redox homeostasis. Western blotting, cell cycle distribution assay, and DOX uptake assay were performed to further elucidate the possible antineoplastic mechanism of SSD. Finally, a subcutaneous MCF7/DOX cell xenografted model in nude mice was established to identify the in vivo anticarcinogenic effect of SSD combined with DOX. ResultsSSD significantly inhibited cell viability, proliferation, and clone formation, enhancing DOX's anticancer efficacy in vitro and in vivo. Mechanistically, SSD reduced STAT1, NQO1, and PGC-1α protein levels, leading to cellular redox imbalance, excessive ROS generation, and depletion of GSH, NADPH, and NADH. SSD induced DNA damage by disrupting redox homeostasis, resulting in G0/G1 phase cell cycle arrest. Additionally, SSD increased DOX accumulation in BC cells via inhibiting P-gp protein expression and efflux activity. ConclusionWe demonstrated for the first time that SSD enhances the sensitivity of chemoresistant BC cells to DOX by disrupting cellular redox homeostasis through inactivation of the STAT1/NQO1/PGC-1α signaling pathway. This study provides evidence for SSD as an adjuvant agent in drug-resistant BC treatment.

Impact of processed and ultra-processed foods on colorectal cancer risk: Mechanisms, dietary factors, and protective compound

Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide, linked to behavioral factors such as a sedentary lifestyle and smoking, environmental factors like pollution, and nutritional factors including a diet rich in red and processed meats. Some foods are associated with potential carcinogenicity, while others act as protective factors. This review aims to report the contribution of processed and ultra-processed foods to the etiopathogenesis of CRC and explore the role of protective diets. The article is an integrative review conducted in PubMed and VHL databases using the descriptors “colorectal cancer” and “processed foods.” Studies published in the last five years addressing the relationship between these foods and CRC development were included. Potentially carcinogenic substances in processed foods, such as heterocyclic amines, nitrosamines, heme iron, industrial fatty acids, aromatic hydrocarbons, sialic acid sugar, and additives like titanium dioxide, were associated with colon and rectal neoplasms. Additional associations were found with the human microbiome, packaging materials, and food preparation methods. Conversely, several food components can protect against CRC. The consumption of processed and ultra-processed foods can significantly increase CRC risk through mechanisms like inflammation, oxidative stress, gene expression changes, and genetic material damage. The intestinal flora profile may be protective against CRC but is altered when processed and ultra-processed foods are included in the diet. Fiber, phytochemicals, and spices present in plant foods are consistently reported to have anticarcinogenic effects.

Extraction, characterization, and assessment of the antioxidant activity of salvia officinalis extracts

Background : One of the biggest and most significant fragrant and medicinal genera in the Lamiaceae family is salvia (sage). Sage infusion can have numerous health advantages, including anti-mycotic, anti-carcinogenic, antidiabetic, antibacterial, antioxidant, anti-inflammatory, and anti-proliferative effects. By lowering free radicals, antioxidants are the chemical compounds that stop or postpone the oxidation process. Lipid oxidation causes color changes, texture problems, odd flavors, nutrient loss, and the creation of hazardous chemicals. Aim of study evaluation of the activity of Salvia officinalis extracts as antioxidants., Methods: Investigated was the chemical detection of active substances. the existence of an active substances and the use of aqueous and alcoholic extracts separately for toxicity test in mice in three concentrations: (10, 20,40 %) it was given orally and the dose ranged between (0.1-0.2 )ml twice a day. Leave the mice for 72 h with monitoring to determine the toxicity of the extracts or not, and evaluation of oxidative stress efficiency by using the DDPH method, Results: The presence of these compounds in extracts of the sage plant, which are compounds that have an effectiveness against cancer cells, which lies in the removal of free radicals (OH. O) they contribute to protecting cells and tissues from active oxygen, The toxicity test results of the aqueous and alcoholic extract showed that they were free of toxicity after oral dosing of mice, The active compounds in the prepared extracts have different polarity, in addition to the use of two different solvents, (water and ethanol), which lead differing results of the effectiveness of the aqueous and alcoholic extracts as antioxidants compared to the gallic acid. Conclusion: The tests for the detection of the active groups of the extracts showed that they are affected by the nature of the solvent in terms of polarity, which affects the type and concentration of the groups extracted and the nature of the extraction, The toxicity test results showed that the aqueous and alcoholic extracts were non-toxic, the results of the antioxidant activity test showed that the alcoholic extract of the sage plant is more effective than the aqueous extract.

The Pros and Cons of Estrogens in Prostate Cancer: An Update with a Focus on Phytoestrogens.

The role of estrogens in prostate cancer (PCa) is shrouded in mystery, with its actions going from angelic to devilish. The findings by Huggins and Hodges establishing PCa as a hormone-sensitive cancer have provided the basis for using estrogens in therapy. However, despite the clinical efficacy in suppressing tumor growth and the panoply of experimental evidence describing its anticarcinogenic effects, estrogens were abolished from PCa treatment because of the adverse secondary effects. Notwithstanding, research work over the years has continued investigating the effects of estrogens, reporting their pros and cons in prostate carcinogenesis. In contrast with the beneficial therapeutic effects, many reports have implicated estrogens in the disruption of prostate cell fate and tissue homeostasis. On the other hand, epidemiological data demonstrating the lower incidence of PCa in Eastern countries associated with a higher consumption of phytoestrogens support the beneficial role of estrogens in counteracting cancer development. Many studies have investigated the effects of phytoestrogens and the underlying mechanisms of action, which may contribute to developing safe estrogen-based anti-PCa therapies. This review compiles the existing data on the anti- and protumorigenic actions of estrogens and summarizes the anticancer effects of several phytoestrogens, highlighting their promising features in PCa treatment.

Promising anticarcinogenic effect of some Nigerian vegetables on cancer cells

Promising anticarcinogenic effect of some Nigerian vegetables on cancer cells

IL-17A Drives Oxidative Stress and Cell Growth in A549 Lung Epithelial Cells: Potential Protective Action of Oleuropein.

IL-17A drives inflammation and oxidative stress, affecting the progression of chronic lung diseases (asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and cystic fibrosis). Oleuropein (OLP) is a polyphenolic compound present in olive oil and widely included in the Mediterranean diet. It exerts antioxidant and anti-inflammatory activities, oxidative stress resistance, and anticarcinogenic effects with a conceivable positive impact on human health. We hypothesized that OLP positively affects the mechanisms of oxidative stress, apoptosis, DNA damage, cell viability during proliferation, and cell growth in alveolar epithelial cells and tested its effect in a human alveolar epithelial cell line (A549) in the presence of IL-17A. Our results show that OLP decreases the levels of oxidative stress (Reactive Oxygen Species, Mitochondrial membrane potential) and DNA damage (H2AX phosphorylation-ser139, Olive Tail Moment data) and increases cell apoptosis in A549 cells exposed to IL-17A. Furthermore, OLP decreases the number of viable cells during proliferation, the migratory potential (Scratch test), and the single cell capacity to grow within colonies as a cancer phenotype in A549 cells exposed to IL-17A. In conclusion, we suggest that OLP might be useful to protect lung epithelial cells from oxidative stress, DNA damage, cell growth, and cell apoptosis. This effect might be exerted in lung diseases by the downregulation of IL-17A activities. Our results suggest a positive effect of the components of olive oil on human lung health.

The preventive effects of diosmin alone or combined with irinotecan on 1,2-dimethylhydrazine-induced colon cancer in rats.

Colorectal cancer, one of the most frequently diagnosed cancers worldwide, has a high mortality rate. Thus, our research aims to examine the preventive effects of diosmin (DIO) alone and in conjunction with the anti-cancer drug irinotecan (camptothecin-11, CPT-11), on 1,2-dimethylhydrazine (DMH)-induced colon cancer (CC) in male Wistar rats. Fifty adult male Wistar rats were categorized into five groups. Group I (Normal) received saline 0.9 orally % as a vehicle once a week for 14 weeks. Group II (DMH) received DMH (20 mg/kg/week) orally dissolved in 0.9% saline for 14 weeks and 1% carboxymethylcellulose (CMC) every other day for the final 10 weeks. Group III (DMH+DIO) received DMH orally for 14 weeks and DIO (10 mg/kg, suspended in 1% CMC) every other day for the final 10 weeks. Group IV (DMH+CPT-11) received DMH orally for 14 weeks and intraperitoneal injection of CPT-11 (3 mg/kg) twice a week for the final 10 weeks. Group V (DMH+DIO+CPT-11) orally received DMH for 14 weeks and both DIO and CPT-11. All treated groups showed a significant reduction (p<0.05) in their elevated serum malondialdehyde levels and significant amelioration (p<0.05) of their lowered activities of colon glutathione-S-transferase (GST) and glutathione reductase (GR) as well as serum glutathione level (GSH). In addition, simultaneous treatment with DIO and CPT-11 led to a significant decrease (p<0.05) in the elevated serum levels of carcinoembryonic antigen (CEA) in rats administered with DMH, as well as a reduction in the colon expression levels of the inflammatory mediator (NF-κB), cell proliferator protein (Ki-67), and proapoptotic protein (p53). These findings suggest DIO, CPT-11, and their combination have anticarcinogenic effects against DMH-induced CC by suppressing oxidative stress, simulating the antioxidant defense system, attenuating the inflammatory effects, and reducing cell proliferation.

Evaluation of Bioactivity of Ethanol and Water Extracts and Determination of Nutrient Concentrations of Laurel (Laurus nobilis) Plants Grown in İzmir Province

This study was conducted to determination of ethanol and water extracts obtained from the leaves of Laurus nobilis (Laurel) plant of the general content by GC-MS analysis, antimicrobial activities of these extracts on some microorganisms, total antioxidant levels (TAS), total oxidant levels (TOS), oxidative stress index (OSI) values, anti-carcinogenic effects on various cell lines and macro and micronutrient concentrations of Laurel (Laurus nobilis) plants cultivated for decorative purposes in parks and gardens of Izmir province of Turkey. TAS, TOS, and OSI values were determined with the aid of Rel Assay Diagnostics kits. In antimicrobial activity analysis, the minimum inhibition concentration (MIC) of the plant extracts against microorganisms was determined by microdilution broth method. Staphylococcus aureus (ATCC 29213), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), Bacillus cereus (ATCC11778), Candida albicans (ATCC 10231) and Candida tropicalis (DSM11953) microorganisms were used in this analysis. Furthermore, cytotoxic activities of plant extracts were determined by XTT method in normal rat fibroblast cell line, HUVEC, and 2 different human cancer cell lines. At the end of the study, it was found that ethanol and water extracts of the Laurel plants had no antimicrobial activity, low oxidative stress index and good antioxidant activity, and moderate cytotoxic activity on experimented cell lines. Nitrogen (N), Phosphorus (P), Potassium (P), Calcium (Ca), Magnesium (Mg), Iron (Fe), Zinc (Zn), Manganese (Mn) and Copper (Cu) concentrations of plant extracts were respectively identified as 1.68% N, 0.72% P, 1.12% K, 2.40% Ca, 0.45% Mg, 147.4 mg/kg Fe, 13.6 mg/kg Zn, 326.3 mg/kg Mn and 27.8 mg/kg Cu.

Phenethyl isothiocyanate inhibits the carcinogenic properties of hepatocellular carcinoma Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways.

Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited effective treatment options. Phenethyl isothiocyanate (PEITC) is a bioactive substance present primarily in the cruciferous vegetables. PEITC has exhibited anti-cancer properties in various cancers, including lung, bile duct, and prostate cancers. It has been demonstrated that PEITC can inhibit the proliferation, invasion, and metastasis of SK-Hep1 cells, while effectively inducing apoptosis and cell cycle arrest in HepG2 cells. However, knowledge of its anti-carcinogenic effects on Huh7.5.1 cells and its underlying mechanism remains elusive. In the present study, we aim to evaluate the anti-carcinogenic effects of PEITC on human HCC Huh7.5.1 cells. MTT assay and colony formation assay was performed to investigate the anti-proliferative effects of PEITC against Huh7.5.1 cells. The pro-apoptosis effects of PEITC were determined by Annexin V-FITC/PI double staining assay by flow cytometry (FCM), mitochondrial transmembrane potential (MMP) measurement, and Caspase-3 activity detection. A DAPI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was conducted to estimate the DNA damage in Huh7.5.1 cells induced by PEITC. Cell cycle progression was determined by FCM. Transwell invasion assay and wound healing migration assay were performed to investigate the impact of PEITC on the migration and invasion of Huh7.5.1 cells. In addition, transcriptome sequencing and gene set enrichment analysis (GSEA) were used to explore the potential molecular mechanisms of the inhibitory effects of PEITC on HCC. Quantitative real-time PCR (qRT-PCR) analysis was performed to verify the transcriptome data. MTT assay showed that treatment of Huh7.5.1 cells with PEITC resulted in a dose-dependent decrease in viability, and colony formation assay further confirmed its anti-proliferative effect. Furthermore, we found that PEITC could induce mitochondrial-related apoptotic responses, including a decrease of mitochondrial transmembrane potential, activation of Caspase-3 activity, and generation of intracellular reactive oxygen species. It was also observed that PEITC caused DNA damage and cell cycle arrest in the S-phase in Huh7.5.1 cells. In addition, the inhibitory effect of PEITC on the migration and invasion ability of Huh7.5.1 cells was assessed. Transcriptome sequencing analysis further suggested that PEITC could activate the typical MAPK, PI3K-Akt, and p53 signaling pathways, revealing the potential mechanism of PEITC in inhibiting the carcinogenic properties of Huh7.5.1 cells. PEITC exhibits anti-carcinogenic activities against human HCC Huh7.5.1 cells by activating MAPK/PI3K-Akt/p53 signaling pathways. Our results suggest that PEITC may be useful for the anti-HCC treatment.

Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice

Introduction: Uncaria tomentosa (Willd. ex Roem. &amp; Schult.) DC. (Rubiaceae) or UT is a medicinal plant with antiviral, antimutagenic, anti-inflammatory and antioxidant properties. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene; this deficiency leads to sarcolemma instability, inflammation, muscle degeneration and fibrosis. Objective: Considering the importance of inflammation to dystrophy progression and the anti-inflammatory activity of UT, in the present study we evaluated whether oral administration of UT extract would ameliorate dystrophy in the mdx mice, a DMD model. Methods: Eight-week-old male mdx mice were submitted to 200 mg/kg body weight daily UT oral administration for 6 weeks. General histopathology was analysed, and muscle tumor necrosis factor α, transforming growth factor-β, myostatin and osteopontin transcript levels were assessed. The ability of mice to sustain limb tension to oppose their gravitational force was measured. Data were analysed with the unpaired Student’s t-test. Results: Morphologically, both untreated and UT-treated animals exhibited internalised nuclei, increased endomysial connective tissue and variations in muscle fibre diameters. Body weight and muscle strength were significantly reduced in the UT-treated animals. Blood creatine kinase was higher in UT-treated compared to untreated animals. In tibialis anterior, myostatin, transcript was more highly expressed in the UT-treated while in the diaphragm muscle, transforming growth factor-β transcripts were less expressed in the UT-treated. Conclusion: While previous studies identified anti-inflammatory, antiproliferative and anticarcinogenic UT effects, the extract indicates worsening of dystrophic muscles phenotype after short-term treatment in mdx mice.