Ehrlich Ascites Carcinoma Model Research Articles

Ehrlich ascites carcinoma provokes renal toxicity and DNA injury in mice: Therapeutic impact of chitosan and maitake nanoparticles.

In this study, the impact of chitosan (CS) and maitake (GF) nanoparticles towards the renal toxicity induced by Ehrlich ascites carcinoma (EAC) in vivo model was conducted. Besides benchmark negative control group, EAC model was constructed by intraperitoneal injection (i.p.) of 2.5 × 106 cells. Alongside positive control, two groups of EAC-bearing mice received 100 mg/kg of CS and GF nanoparticles/body weight daily for 14 days. The kidney function was conducted by measuring urea, creatinine, ions, (anti)/oxidative parameters and DNA damage. Also, measuring immunoreactivity of P53, proliferating cell nuclear antigen (PCNA), and B-cell lymphoma 2 (Bcl-2) and apoptosis protein. The outcomes illustrated notable kidney toxicity, which indicated by elevations in urea, creatinine, oxidative stress, DNA damage and induction of apoptosis. These events were supported by the drastic alteration in kidney structure through histological examination. Administration of CS and GF nanoparticles was able to enhance the antioxidant power, which further reduced oxidative damage, DNA injury, and apoptosis. These results indicated the protective and therapeutic role of biogenic chitosan and maitake nanoparticles against nephrotoxicity.

Vitamin D3 Inhibits the Viability of Breast Cancer Cells In Vitro and Ehrlich Ascites Carcinomas in Mice by Promoting Apoptosis and Cell Cycle Arrest and by Impeding Tumor Angiogenesis.

The incidence of aggressive and resistant breast cancers is growing at alarming rates, indicating a necessity to develop better treatment strategies. Recent epidemiological and preclinical studies detected low serum levels of vitamin D in cancer patients, suggesting that vitamin D may be effective in mitigating the cancer burden. However, the molecular mechanisms of vitamin D3 (cholecalciferol, vit-D3)-induced cancer cell death are not fully elucidated. The vit-D3 efficacy of cell death activation was assessed using breast carcinoma cell lines in vitro and a widely used Ehrlich ascites carcinoma (EAC) breast cancer model in vivo in Swiss albino mice. Both estrogen receptor-positive (ER+, MCF-7) and -negative (ER-, MDA-MB-231, and MDA-MB-468) cell lines absorbed about 50% of vit-D3 in vitro over 48 h of incubation. The absorbed vit-D3 retarded the breast cancer cell proliferation in a dose-dependent manner with IC50 values ranging from 0.10 to 0.35 mM. Prolonged treatment (up to 72 h) did not enhance vit-D3 anti-proliferative efficacy. Vit-D3-induced cell growth arrest was mediated by the upregulation of p53 and the downregulation of cyclin-D1 and Bcl2 expression levels. Vit-D3 retarded cell migration and inhibited blood vessel growth in vitro as well as in a chorioallantoic membrane (CAM) assay. The intraperitoneal administration of vit-D3 inhibited solid tumor growth and reduced body weight gain, as assessed in mice using a liquid tumor model. In summary, vit-D3 cytotoxic effects in breast cancer cell lines in vitro and an EAC model in vivo were associated with growth inhibition, the induction of apoptosis, cell cycle arrest, and the impediment of angiogenic processes. The generated data warrant further studies on vit-D3 anti-cancer therapeutic applications.

Peanut Resveratrol Inhibits COX-2 in Ehrlich Ascites Carcinoma In vivo Model

Background: The primary goal of researchers interested in the field of oncology continues to be the development of a new anti-cancer medicine with minimal side effects. Due to their minimal toxicity and impressive performance, natural source-mediated anti-cancer treatments are attracting a lot of attention. Objective: The purpose of the current work was to extract and purify resveratrol from local Leguminosae, such as peanut, beans, cowpea, lupine, fava bean, and soybean, and then assess its cyclooxygenase- 2 (COX-2) inhibition. The aim was then to evaluate the anticancer potential of extracted resveratrol individually or combined with doxorubicin against Ehrlich ascites carcinoma (EAC) model. Methods: Resveratrol was extracted and purified using a silica gel column. The inhibition study of extracted resveratrol was conducted against COX-2 in vitro. Then, the anti-proliferation impact of resveratrol alone or combined with doxorubicin was evaluated against the previously established EAC model. Apoptotic/anti-apoptotic genes and cell cycle arrest were investigated. Results: After being extracted from peanuts, resveratrol inhibited COX-2 in vitro competitively with an inhibition constant (Ki) of 0.545 μM, which is extremely close to the theoretically predicted value (0.48 μM) from molecular docking. Further, resveratrol obviously inhibited COX-2 in vivo. Importantly, resveratrol was able to cause apoptosis by upregulating Bax and downregulating the anti-apoptotic gene Bcl-2, either by itself or in combination with doxorubicin. Additionally, resveratrol's ability to stop the cell cycle is evidence of its COX-2-inhibiting antiproliferative properties. Conclusion: Resveratrol exhibits anticancer potential via inhibition of COX-2, and it could be appropriate for combinational therapy in vivo.

Характеристика модели асцитной карциномы Эрлиха и перспективы ее применения в экспериментальной фармакологии ветеринарных препаратов

The article provides an overview of the most significant works of domestic and foreign authors devoted to the Ehrlich ascites carcinoma biological model. The analysis of the available literary sources showed that despite the long history of the existence of this model and its application in biomedical research, it has not yet become widespread in veterinary medicine. It should be noted that the Ehrlich ascites carcinoma model has a number of peculiarities that allow it to be used for the needs of veterinary medicine, in particular, experimental pharmacology at the stage of drug design and its preclinical testing. The high resistance of malignant cells and tumor survival in experimental animals, as well as the ease of its cultivation and relatively rapid tumor growth, make this model a convenient biological object for research. The effect of tumor cells on the body of the animal with a tumor leads to a change in a number of biochemical indicators of various tissues and organs, and a general toxic effect. In this case, an imbalance of the free-radical and antioxidant systems is observed, the body is exposed to oxidative stress. The immune system under the effect of Ehrlich ascites carcinoma also undergoes a number of changes. Thus, in response to the development of tumor-induced pathological processes, recruitment of immunocompetent cells and an antitumor immune response are observed, which at the same time is suppressed as carcinoma cells grow under the action of immunosuppressive physiologically active compounds produced by the tumor, escape of tumor cells from immunological surveillance and remodelling of immune cells in the tumor microenvironment. These processes lead to suppression of the immune system and as a result to the death of animals. These peculiarities make it possible to use the Ehrlich transplantable ascites carcinoma model for testing new veterinary drugs with potential antiblastoma, immunomodulatory, antitoxic properties, as well as medicinal formulations for restoring biochemical indicators and redox homeostasis under conditions of tumor-induced immunosuppression and chronic inflammatory process, and also to study the mechanisms of cell adaptation, including the immune system, under the action of carcinogenesis factors.

Muc2-дефицитные мыши как модель хронического воспаления

The article provides an overview of the most significant works of domestic and foreign authors devoted to the Ehrlich ascites carcinoma biological model. The analysis of the available literary sources showed that despite the long history of the existence of this model and its application in biomedical research, it has not yet become widespread in veterinary medicine. It should be noted that the Ehrlich ascites carcinoma model has a number of peculiarities that allow it to be used for the needs of veterinary medicine, in particular, experimental pharmacology at the stage of drug design and its preclinical testing. The high resistance of malignant cells and tumor survival in experimental animals, as well as the ease of its cultivation and relatively rapid tumor growth, make this model a convenient biological object for research. The effect of tumor cells on the body of the animal with a tumor leads to a change in a number of biochemical indicators of various tissues and organs, and a general toxic effect. In this case, an imbalance of the free-radical and antioxidant systems is observed, the body is exposed to oxidative stress. The immune system under the effect of Ehrlich ascites carcinoma also undergoes a number of changes. Thus, in response to the development of tumor-induced pathological processes, recruitment of immunocompetent cells and an antitumor immune response are observed, which at the same time is suppressed as carcinoma cells grow under the action of immunosuppressive physiologically active compounds produced by the tumor, escape of tumor cells from immunological surveillance and remodelling of immune cells in the tumor microenvironment. These processes lead to suppression of the immune system and as a result to the death of animals. These peculiarities make it possible to use the Ehrlich transplantable ascites carcinoma model for testing new veterinary drugs with potential antiblastoma, immunomodulatory, antitoxic properties, as well as medicinal formulations for restoring biochemical indicators and redox homeostasis under conditions of tumor-induced immunosuppression and chronic inflammatory process, and also to study the mechanisms of cell adaptation, including the immune system, under the action of carcinogenesis factors.

3,5,7-trihydroxyflavone restricts proliferation of androgen-independent human prostate adenocarcinoma cells by inducing ROS-mediated apoptosis and reducestumour growth.

Flavonoids are among the largest groups of secondary metabolites. Studies suggestthat dietary intake of flavonoids reducesthe risk of cancer. 3,5,7-trihydroxyflavone (THF) belongs to the flavone class of flavonoids and potentially inhibits the growth of many cancers; however, it is unexplored in prostate cancer. This study reports the antiproliferative potential of THF in prostate cancer cell line via reactive oxygen species (ROS)-mediated cascades and examines the tumour reduction potential in swiss albino mice. The potency of THF was evaluated by employing cytotoxicity assays and wound healing assays. Cell cycle, ROS, mitochondrial membrane potential (MMP), and Annexin-V-FITC assay were performed using a flow cytometer. In vivo, anticancer potential was achieved using the mice Ehrlich Ascites Carcinoma (EAC) model. THF inhibits cell growth with IC50 of 64.30 µM (MTT), 81.22 µM (NRU) and 25.81 µM (SRB), substantiated by cell migration assay. Cell-cycle analysis revealed that THF increases the subdiploid population. Furthermore, the Annexin-V-FITC assay evoked a significant induction of late apoptosis at a higher concentration of THF. THF also disrupts MMP, caused by an increased generation of ROS. In the EAC model, THF significantly inhibits tumour growth and increases the percent survival of mice and ROS levels in EAC cells. Hence, it may be concluded that THF might execute its antiproliferative effect via inducing ROS generation and could be a promising lead for preclinical and clinical validations.

Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis.

To explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR). We used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR. In EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin. Dietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR.

The flavonoid hesperidin methyl chalcone as a potential therapeutic agent for cancer therapy: Molecular docking, in vitro cytotoxicity, and in vivo antitumor activity

Hesperidin methyl chalcone (HMC) is a methylation product of the flavanone hesperidin, a flavonoid derived from citrus fruits. Many reports have emphasized the analgesic, anti-inflammatory and antioxidant properties of HMC. However, the anticancer potential of HMC has not been fully elucidated. The objective of this study was to assess the possible anticancer potential of HMC. MTT assay was carried out to assess the in vitro cytotoxicity of HMC against using A549 cancer cell line. In addition, the in vivo antitumor activity of HMC was screened against murine Ehrlich ascites carcinoma (EAC) model, in terms of tumor volume, tumor weight, life span, hematological and biochemical parameters, and compared with that of the anticancer agent, hesperetin. HMC was efficient to suppress the cell viability of A549 cancer cells with an IC50 value of 51.12 µM, which was comparable to that of the anticancer agent hesperetin (IC50 = 49.12 µM). Similarly, in Ehrlich ascites carcinoma model, HMC significantly inhibited the growth of Ehrlich ascites carcinoma with mutual increase in the life span of HMC-treated mice, compared to EAC control. Most importantly, HMC showed a good safety profile as evidenced by restoring hematological profile count of RBCs, WBCs, and hemoglobin to the normal levels. HMC also efficiently reduced the oxidative stress in EAC-bearing mice via increasing the levels of GSH, SOD and Catalase. Collectively, HMC exerted a potent anticancer activity and data presented in this work suggest the usefulness of HMC as a promising candidate in cancer therapy.

Potential use of nanoformulated ascorbyl palmitate as a promising anticancer agent: First comparative assessment between nano and free forms

The aim of the present study is to evaluate, for the first time, the anticancer activity of a stable nanoformulation of ascorbyl palmitate (APnp) and investigate its therapeutic action as well as its mechanism against Ehrlich ascites carcinoma (EAC)-bearing mice in comparison with native AP. AP was loaded into pluronic nanoparticles, fully characterized and then studied as an anticancer agent using EAC model. The APnp were spherical and attained a small size of 220 ± 9 nm and a zetapotential of −41.16 ± 2 mV. The release profile of the AP from the nanoparticles was around 72% within the first 2 h and the rest of the drug amount was released sustainably within 9 days. The results of the present study demonstrated that APnp treatment destroyed tumors with inhibition of proliferation by inhibiting signal transducer and activator of transcription 3 (STAT3) pathway leading to induction of apoptosis and cell cycle arrest at G2/M phase as well as preventing metastasis and invasion. Moreover, APnp significantly elevated antioxidant levels [superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH)], and significantly decreased the levels of oxidative stress biomarkers [malondialdehyde (MDA) and nitric oxide (NO)]. Besides, mitochondrial and nuclear degeneration in cancer cells was demonstrated by an electron microscope to be more severe in the case of using our newly-developed APnp. The present study revealed the superiority of APnp as a potent anticancer agent over free AP via increasing its bioavailability and specificity towards cancer cells.

In vitro and in vivo anticancer potential and molecular targets of the new colchicine analog IIIM-067

ObjectiveThe current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells. MethodsSulforhodamine B (SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide (IIIM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4′,6-diamidino-2-phenylindole (DAPI) and annexin V/propidium iodide. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma (EAC) and Ehrlich solid tumor models were conducted using Swiss albino mice. ResultsIIIM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of IIIM-067 toward A549 cells was higher among other cancer cell lines, with a selectivity index (SI) value of 2.28. IIIM-067 demonstrated concentration- and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and 0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells (SI > 1) than the parent compound colchicine (SI = 1). IIIM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. IIIM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP (100% in control to 5.6% at 0.4 μmol/L). The annexin V-FITC assay demonstrated 78% apoptosis at 0.4 μmol/L. IIIM-067 significantly (P < 0.5) induced the expression of various intrinsic apoptotic pathway proteins, and it differentially regulated the PI3K/AKT/mTOR signaling pathway. Furthermore, IIIM-067 exhibited remarkable in vivo anticancer activity against the murine EAC model, with tumor growth inhibition (TGI) of 67.0% at a dose of 6 mg/kg (i.p.) and a reduced mortality compared to colchicine. IIIM-067 also effectively inhibited the tumor growth in the murine solid tumor model with TGI rates of 48.10%, 55.68% and 44.00% at doses of 5 mg/kg (i.p.), 6 mg/kg (i.p.) and 7 mg/kg (p.o.), respectively. ConclusionIIIM-067 exhibited significant anticancer activity with reduced toxicity both in vitro and in vivo and is a promising anticancer candidate. However, further studies are required in clinical settings to fully understand its potential.

Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach

Albeit its established efficacy as an anti-hyperlipidemic agent, pitavastatin (PIT) has been shown to have other various therapeutic effects. One of these effects is the anti-cancer activity against hepatocellular carcinoma (HCC). This effect has been evaluated in this study for the first time via its oral delivery loaded in bilosomes both in vitro in hepatocellular carcinoma (HCC) cell line; HepG2 and in vivo in an Ehrlich ascites carcinoma (EAC) model. Moreover, the impact of surface modification of bilosomes with lactoferrin (LF) as an active targeting ligand for HCC was investigated. Bilosomes were prepared by thin-film hydration and different molar phospholipid to bile salt ratios were used to optimize the bilosomal formulation. The molar phospholipid to bile salt ratio was adjusted to 4:1 at pH 7.4. LF-coated bilosomes possessed a particle size, PDI, entrapment efficiency, and zeta potential of 112.28 nm ± 6.35, 0.229 ± 0.06, 90.56% ± 3.22, and −7.86 mV ± 1.13, respectively. LF-coated bilosomes also increased permeation of PIT when tested on Caco-2 cells by 3.1-folds (compared to uncoated ones or free PIT solution). It also improved the cytotoxicity of HepG2 spheroids 44-folds more than PIT-free solution. RT-PCR analysis showed that LF-coated PIT-loaded bilosomes caused an improvement (2-fold increase) in the apoptotic potential of PIT mediated by caspase-3. In conclusion, the optimized LF-coated PIT-loaded bilosomes were cytotoxic to HCC with improved hepatocytes permeation and cellular uptake. Thus, the proposed formula could be a promising treatment for HCC.

Chemopreventive effects of Prunus cerasus L. against human cancer cells & ascites mice models and its phytochemical investigation by LC-Q-TOF-MS/MS

BackgroundBerries, including cherries and their derived distinctive bioactive leads, are explored for the establishment of therapeutic supplements, owing to their versatile biological applications accompanied with less or no side effects to normal cells. The current research work aimed to identify various phytocomponents of P. cerasus fruit extract (PcMFE) and investigate its chemopreventive properties employing cellular assays coupled with experimental Ascites mice models. MethodLC-ESI-Q-TOF-MS (HRMS) approaches were used for chemoprofiling of P. cerasus methanolic fruit extract (PcMFE). After testing for scavenging capacities on DPPH, radical & lipid peroxidation, the In-vitro anticancer potential was investigated against five distinct human cancer cell lines A-549, THP-1, MCF-7, PC-3 and NCI-H322 using MTT and SRB assays. In case of in-vivo antitumor assessment, PcMFE was investigated against Ehrlich Ascites Carcinoma (EAC) and Methylcholanthrene induced Ascites (Meth-A) experimental mice models. ResultsHRMS analysis of PcMFE resulted in identification of 59 compounds belonging to diverse chemical classes. Besides significant antioxidant potential, PcMFE at 50 µg/ml dose blocked 40–100% growth of various cancer cell lines, with maximum (100% growth inhibition) against NCI-H322 showing an IC50 of 5.59 µg/ml and 5 µg/ml respectively in SRB and MTT assays. Execution of apoptosis induced by PcMFE in NCI-H322 cancer cells revealed an increased population of apoptotic cells evidenced through nuclear morphology studies. Moreover, intraperitoneal administration of PcMFE at 200 mg/kg body weight reported 72.31% and 68.69% tumor growth inhibition in EAC & Meth-A mice model, respectively. ConclusionsThe present study exhibited that P- cerasus fruit is a valuable source of diverse functional metabolites and may facilitate development of chemopreventive supplements.

Processed Cheeses Fortified by Laurus Nobilis L. Extract Nanoemulsion Ameliorate Hyperhomocysteinemia in Ehrlich Ascites Carcinoma Model

Processed Cheeses Fortified by Laurus Nobilis L. Extract Nanoemulsion Ameliorate Hyperhomocysteinemia in Ehrlich Ascites Carcinoma Model

A cytostatic drug from the class of triazine derivatives: Its properties in aqueous solutions, cytotoxicity, and therapeutic activity

We present a comprehensive study of a water-soluble substance from the class of triazine derivatives alkylating agents. The performed physicochemical investigations of this cytostatic drug’s aqueous solutions include the measurements of density, viscosity, speed of sound, refraction index, stability, solubility, distribution between water and octan-1-ol, as well as electronic structure calculations and molecular dynamics modelling. Biologically, the substance was investigated for its cytotoxicity as well as in vitro (on Capan-2 and SK-MEL-1 cell lines) and in vivo (transplantable Ehrlich ascites carcinoma model) therapeutic activity.

Antitumor and antiangiogenic effects of Tonantzitlolone B, an uncommon diterpene from Stillingia loranthacea.

Natural products have played a pivotal role for the discovery of anticancer drugs. Tonantzitlolones are flexibilan-type diterpenes rare in nature; therefore, few reports have shown antiviral and cytotoxic activities. This study aimed to investigate the in vivo antitumor action of Tonantzitlolone B (TNZ-B) and its toxicity. Toxicity was evaluated in mice (acute and micronucleus assays). Antitumor activity of TNZ-B (1.5 or 3mg/kg intraperitoneally - i.p.) was assessed in Ehrlich ascites carcinoma model. Angiogenesis and reactive oxygen species (ROS) and nitric oxide (NO) production were also investigated, in addition to toxicological effects after 7-day treatment. The LD50 (lethal dose 50%) was estimated at around 25mg/kg (i.p.), and no genotoxicity was recorded. TNZ-B reduced the Ehrlich tumor's volume and total viable cancer cell count (p < 0.001 for both). Additionally, TNZ-B reduced peritumoral microvessel density (p < 0.01), suggesting antiangiogenic action. Moreover, a decrease was observed on ROS (p < 0.05) and nitric oxide (p < 0.001) levels. No significant clinical findings were observed in the analysis of biochemical, hematological, and histological (liver and kidney) parameters. In conclusion, TNZ-B exerts antitumor and antiangiogenic effects by reducing ROS and NO levels and has weak in vivo dose-repeated toxicity. These data contribute to elucidate the antitumor action of TNZ-B and point the way for further studies with this natural compound as an anticancer drug.

Is Amygdalin Outcomes Weighing Detriments of Sorafenib Treatment In Female Mice With Kidney Injury Induced By Ehrlich Ascites Carcinoma Model? Preliminary study

Aim: Nowadays, attention is intensifying in using natural sources of real antitumor agents that breed fewer side effects than unadventurous chemotherapeutic drugs. The Ehrlich ascites carcinoma (EAC) model is a spontaneous adenocarcinoma that can use to induce cancer in the targeted organ. This preliminary study is implemented to weigh the best choice for cancer treatment with fewer side effects and rule out the concomitant use of targeted drugs against kidney injury in female mice induced by EAC. Material and methods: The mice were apportioned into seven groups. The most affected parameters in the EAC mice model as Kidney functions and hematological parameters were measured. Furthermore, to exact unearth the values of two drugs, histopathological studies were further evaluated. Results: The results showed that the mice with EAC exhibited kidney functions with alterations of hematological parameters. Co-administration of vitamin B17 and sorafenib restored the kidney functions in serum. Ample histopathological variations were detected in kidney sections in EAC as marked damage and degenerated glomerular atrophy and necrosis of renal corpuscle and tubules. A moderate improvement in kidney sections noted in sorafenib (SOR) group as a mild degeneration in both renal corpuscles and renal tubules in addition to congestion of renal blood vessels were improved contrary to B17 group that improved better than SOR. Conclusion: It could be concluded that B17 has a potential defensive role against EAC cells-induced kidney toxicity rather than the undesirable effect of SOR in the tested parameters.

Suppression of Molecular Targets and Antiproliferative Effect of Citronellal on Triple-Negative Breast Cancer Cells.

Triple-Negative Breast Cancer (TNBC) requires targeted therapies to better manage and prevent metastatic mammary gland tumors. Due to the resistance problem associated with the approved drugs, researchers are now focusing on phytochemicals for the treatment of TNBC as they possess pleiotropic mode of action and fewer side effects. To investigate the antiproliferative effect of citronellal on triple-negative breast cancer cells. Anticancer potential of citronellal was explored by employing SRB, MTT, and NRU antiproliferative assay. Further, the effect of citronellal was observed on molecular targets (Tubulin, COX-2, and LOX-5) utilizing in vitro and in silico methods. Furthermore, the efficacy of citronellal was examined on Ehrlich Ascites Carcinoma cells. In addition, the safety profiling of it was observed at 300 and 1000 mg/kg of body weight in mice. Citronellal suppresses the growth of MDA-MB-231 cells by more than 50% in NRU assay and ~41% and 32% in SRB and MTT assay, respectively. Further, citronellal's effect was observed on molecular targets wherein it suppressed LOX-5 activity (IC50 40.63±2.27 μM) and prevented polymerization of microtubule (IC50 63.62 μM). The result was more prominent against LOX-5 as supported by molecular docking interaction studies, but a non-significant effect was observed at the transcriptional level. The efficacy of citronellal was also determined in Ehrlich Ascites Carcinoma (EAC) model, wherein it inhibited the growth of tumor cells (45.97%) at 75 mg/kg of body weight. It was non-toxic up to 1000 mg/kg of body weight in mice and did not cause significant lysis of erythrocytes. These observations could provide experimental support for citronellal to be used as a chemopreventive agent for breast cancer.

Anticancer Effects of Combination of Indole-3-Carbinol and Hydroxychloroquine on Ehrlich Ascites Carcinoma via Targeting Autophagy and Apoptosis

Indole-3-carbinol (I3C) is an active component of cruciferous vegetables which is considered a promising antineoplastic agent. This study aimed to assess I3C antineoplastic activity alone and with hydroxychloroquine (HCQ) on Ehrlich ascites carcinoma (EAC) model. Eighty female mice were divided into six groups wherein all groups except groups I and II received EAC cells (106 cells/mouse i.p.). Group I, served as control; group II served as I3C; group III served as EAC; groups IV and V received I3C (250 mg/kg body weight oral), and HCQ (60 mg/kg body weight i.p.) respectively; GVI received both I3C and HCQ. Antitumor response markers, serum, hepatic and renal biochemical parameters, histopathological changes, as well as autophagy and apoptosis markers in EAC cells were analyzed. The combination of I3C and HCQ showed the best antitumor responses with increased survival time and ameliorated biochemical parameters. Moreover, I3C upregulated LC3B and downregulated p62 gene expression in EAC cells. Furthermore, I3C combined with HCQ induced apoptosis by highly upregulating cleaved caspase-3 and Bax while downregulating Bcl-2 proteins expression in EAC cells in comparison with each drug alone. In conclusion, I3C combined with HCQ exhibited better antitumor activities than each drug alone via targeting autophagy and apoptosis.

The Anticancer Efficacy of Plasma-Oxidized Saline (POS) in the Ehrlich Ascites Carcinoma Model In Vitro and In Vivo.

Cold physical plasma, a partially ionized gas rich in reactive oxygen species (ROS), is receiving increasing interest as a novel anticancer agent via two modes. The first involves its application to cells and tissues directly, while the second uses physical plasma-derived ROS to oxidize liquids. Saline is a clinically accepted liquid, and here we explored the suitability of plasma-oxidized saline (POS) as anticancer agent technology in vitro and in vivo using the Ehrlich Ascites Carcinoma (EAC) model. EAC mainly grows as a suspension in the peritoneal cavity of mice, making this model ideally suited to test POS as a putative agent against peritoneal carcinomatosis frequently observed with colon, pancreas, and ovarium metastasis. Five POS injections led to a reduction of the tumor burden in vivo as well as in a decline of EAC cell growth and an arrest in metabolic activity ex vivo. The treatment was accompanied by a decreased antioxidant capacity of Ehrlich tumor cells and increased lipid oxidation in the ascites supernatants, while no other side effects were observed. Oxaliplatin and hydrogen peroxide were used as controls and mediated better and worse outcomes, respectively, with the former but not the latter inducing profound changes in the inflammatory milieu among 13 different cytokines investigated in ascites fluid. Modulation of inflammation in the POS group was modest but significant. These results promote POS as a promising candidate for targeting peritoneal carcinomatosis and malignant ascites and suggest EAC to be a suitable and convenient model for analyzing innovative POS approaches and combination therapies.

Biochemical Evaluation of Antitumor Activity of Vitamin B17 Alone or in Combination with Platinum Based Drugs Against Ehrlich Ascites Carcinoma in Female Rats

Chemotherapeutic agents are associated with many side effects. Consequently, much research is interested in the discovery of natural phytochemical compounds that can be used in the prevention and/or treatment of cancer. Ehrlich ascites carcinoma (EAC) model was used to indicate the effectiveness of some chemotherapy and plant sources against cancer due to its similarity with human tumors. The present study was undertaken to investigate antitumor and antioxidant effects of vitamin B17 beside platinum-based drugs in EAC-bearing female rats. Animals were randomly distributed into seven groups (n=7) as follows: Group A, negative control. Group B, positive control that was injected by EAC cells as a cancer model. Group C, EAC-bearing rats were treated with cisplatin. Group D, rats with EAC and were treated by a single dose of oxaliplatin. Group E, rats with EAC and were treated with vitamin B17 (VB17). Group F, rats with EAC and were treated with cisplatin plus vitamin B17. Group G, EAC-bearing rats that were treated by single-dose oxaliplatin plus VB17. One week after the beginning of treatments, blood samples were collected and tumor markers (AFP, CEA, CA19-9, TPA, and LDH), as well as antioxidants biomarkers (SOD, CAT, GSH, and MDA), were measured. Liver and kidney functions were evaluated. Besides, histopathological examination was performed to evaluate antitumor activity and side effects of used drugs on hepatic and renal tissues. Results showed that administration of VB17 alone or in combination with cisplatin or oxaliplatin led to a decrease of tumor markers together with enhancement of antioxidant indicators compared with EAC-bearing rats. Statistical analysis showed a significant (P<0.05) increase in the activities of ALT, AST, ALP accompanied by an increase in the serum levels of creatinine, BUN, and total bilirubin in cisplatin and oxaliplatin treated groups, thus confirming their toxic effects on hepatocytes and renal cells. These findings were supported by histopathological alterations in these groups. VB17 treated groups showed improvement in the studied parameters. From the current study, it could be concluded that vitamin B17 possesses anticancer and antioxidant activities that justify its traditional use, and its potential hepatoprotective effect and kidney ameliorative role.