Ehrlich Ascites Carcinoma Cells Research Articles

Design, synthesis and X‐ray structural studies of novel [acetonitrile‐benzyl‐3‐N‐(2, 4 dihydroxyphenylmethylene) hydrazinecarbodithioato‐κ3‐N′, S, O] nickel(ll) complex that potently inhibit cell proliferation through regulation of apoptosis related genes

Nickel is a fundamental element for healthy life for human and higher animals. For biological importance, its complexation with bioactive ligand is worth to be studied with the aim to understand its function. Using mouse peritoneal cancer model, MTT colorimetric assay and anticancer activity analysis, we examined the role of nickel(ll) complex in growth inhibition of cancer cells. A novel nickel(ll) complex was synthesized and characterized using physico‐chemical and spectroscopic techniques. The study indicated that both the ligand and complex were capable of inhibiting Ehrlich Ascites Carcinoma (EAC) cells growth by 28.21% and 44.52%, respectively, when administered 0.3 mg/kg/day body weight intraperitoneally for five consecutive days in Swiss Webstar mice. Determination the LD50 of the complex (55 mg/kg) allowed adjusting the dose as 2.75 mg/kg and upon administration, inhibition increased to 69.36%. The ligand and complex have shown an inhibitory effect in the range of 4.86%–67.3% and 6.1%‐ 89.37%, respectively, against EAC cells (concentration range of 31.25–500 μg/ml) in RPMI‐1640 medium as determined by MTT colorimetric assay. Apoptotic cell morphological alteration was determined through optical and fluorescence microscopy. Up regulation of P53, Bax, Cas‐8, Cas‐3 and Fas and down regulation of NF‐kB and Bcl‐2 gene expression were observed in the cells treated with the nickel(ll) complex for five consecutive days. In conclusion, the newly synthesized nickel(ll) complex has shown anti‐proliferative activity and can further be optimized to be used as a lead molecule for anticancer drug.

Effects of low-level combined static and weak low-frequency alternating magnetic fields on cytokine production and tumor development in mice

ABSTRACTWe investigated the effects of weak combined magnetic fields (MFs) produced by superimposing a constant MF (in the range 30 - 150 µT) and an alternating MF (100 or 200 nT) on cytokine production in healthy Balb/C male mice exposed 2 h daily for 14 days. The alternating magnetic field was a sum of several frequencies (ranging from 2.5 - 17.5 Hz). The frequencies of the alternating magnetic field were calculated formally based on the cyclotron resonance of ions of free amino acids (glutamic and aspartic acids, arginine, lysine, histidine, and tyrosine). The selection of different intensity and frequency combinations of constant and alternating magnetic fields was performed to find the optimal characteristics for cytokine production stimulation in immune cells. MF with a constant component of 60 μT and an alternating component of 100 nT, which was a sum of six frequencies (from 5 to 7 Hz), was found to stimulate the production of tumor necrosis factor-α, interferon-gamma, interleukin-2, and interleukin-3 in healthy mouse cells and induce cytokine accumulation in blood plasma. Then, we studied the effect of this MF on tumor-bearing mice with solid tumors induced by Ehrlich ascite carcinoma cells by observing tumor development processes, including tumor size, mouse survival rate, and average lifespan. Tumor-bearing mice exposed to a combined constant magnetic field of 60 μT and an alternating magnetic field of 100 nT containing six frequencies showed a strong suppression of tumor growth with an increase in survival rate and enhancement of average lifespan.

Inhibitory potential of Hydroxychavicol on Ehrlich ascites carcinoma model and in silico interaction on cancer targets

Hydroxychavicol (HC), a major phenolic derivative isolated from the leaves of Piper betle L. is well known for its antibacterial, antifungal and antimutagenic properties. The present study evaluated the in vivo antitumor activity of HC against Ehrlich Ascites Carcinoma (EAC) cells in Swiss albino mice and in silico interaction of HC with the receptors involved in the cancer. Hydroxychavicol (200 and 400 mg/kg bw) was orally administered for 21 consecutive days and was effective in inhibiting the tumor growth in ascitic mouse model. HC consistently reduced the tumor volume, viable cell count, lipid peroxidation and elevated the life span of HC treated mice. Besides the hematological profiles, SGOT and SGPT levels reverted back to normal and oxidative stress markers GSH, SOD and CAT also increased in HC treated groups. In silico docking analysis revealed that HC possessed potent antagonist activity against all the cancer targets demonstrating its inhibitory activity.

Grape seeds and skin induce tumor growth inhibition via G1-phase arrest and apoptosis in mice inoculated with Ehrlich ascites carcinoma.

Chemoprevention or intervention of cancer by means of natural dietary components has shown great promise in controlling malignancy. This study was conducted to investigate the chemopreventive effects of grape seeds (GSE) combined with grape skin (GSK) in mice that were inoculated with Ehrlich ascites carcinoma, and to elucidate the underlying mechanisms. GSE + GSK were mixed with the standard diet and supplemented to mice 14 d before Ehrlich ascites carcinoma cell inoculation and continued throughout the experiment. Tumor growth was monitored and cell cycle progression and apoptotic effect of GSE + GSK on tumor cells were evaluated. GSE + GSK intake prevented tumor development in 47% of the animals. Tumor volume and weight were markedly reduced by 93.9 % and 86.3 %, respectively, compared with tumor-bearing mice that were untreated with these agents. GSE + GSK treatment caused a marked increase in the percentage of apoptotic tumor cells as evaluated by flow cytometry and confirmed by histopathologic and electron microscopy examinations. GSE + GSK also caused significant cell cycle arrest at the G1 phase, activation of caspase-3, increase in p53 and Bax expression, and decrease in B-cell lymphoma 2 expression and B-cell lymphoma 2:Bax ratio in tumor cells. Furthermore, the induction of apoptosis and cell proliferation inhibition was indicated immunohistochemically as shown by modulating p53 and Ki67 expression. The results of this study clearly showed that the combination of GSE and GSK represents a potent chemopreventive and anticancer agent in a mice model of Ehrlich carcinoma. The mechanisms that underlie the effects of these agents include cell cycle arrest, induction of apoptosis, and inhibition of cell proliferation. These findings suggest that GSE + GSK may represent a natural, novel, adjuvant therapeutic strategy for chemoprevention of the growth of solid tumors.

WITHDRAWN: Purification and characterizations of a new mannose specific lectin from Bangladeshi cultivated sword bean with antiproliferative activities against Ehrlich ascites carcinoma cells in vivo in mice

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A Study of the Cytotoxic Effect of Microcapsules and Their Constituent Polymers on Macrophages and Tumor Cells.

We studied the effect of different concentrations of polyelectrolytes poly(allylamine hydrochloride) (PAH) and polystyrene sulfonate (PSS) as well as the effects of microcapsules coated with these polymers on survival of Ehrlich ascites carcinoma cells and mouse peritoneal macrophages and on ROS production by phagocytes. PAH reduced viability of Ehrlich ascites carcinoma in a concentration-dependent manner (LD50=12-15 μg/ml). This effect was presumably determined by its ability to bind phosphates, thereby depleting the culture medium. At the same time, PAH did not affect the viability of macrophages. PSS produced no cytotoxic effect on the examined cells. Polyelectrolyte capsules with the shell architectonics (PAH/PSS)3 and (PAH/PSS)3PAH in the examined concentration range had no effect on the viability of macrophages and tumor cells. PAH microcapsules with positively charged surface much more rapidly and more intensively activated macrophages. The chemiluminescence response directly depended on the amount of capsules in the solution.

Evaluation of antitumor activity of Urena lobata against Ehrlich ascites carcinoma treated mice

The search for cancer therapy with natural products continues to be a global effort. Many natural products have been tested globally against various cancer cell lines. Urena lobata Linn. (U. lobata) has been used as an ingredient in various formulations of traditional medicines for the treatment of cancers. The present study was undertaken to investigate the antitumor activity of the methanol (MEUL) and aqueous (AEUL) extracts of the U. lobata whole herb in Swiss Albino mice against Ehrlich ascites carcinoma (EAC) cell line. Both extracts were administered orally (200 mg/kg and 400 mg/kg) for 13 consecutive days. After 24 h of the last dose, the animals were scarified. The antitumor effect of the MEUL and AEUL was determined by evaluating the median survival time (days), %ILS, tumor volume, viable tumor cell count, non-viable tumor cell count and tumor weight (g) and hematological parameters of EAC-bearing mice. Both MEUL and AEUL showed significant decrease in tumor volume, the viable cell count, tumor weight, elevated mean survival time, %ILS and non-viable cell count. Hematological profile such as RBC, WBC, and haemoglobin count was reverted to normal level in treated mice. In conclusion, MEUL (400 mg/kg) showed prominent antitumor activity against EAC treated mice.

EVALUATION OF ANTICANCER ACTIVITY OF CUCUMIS CALLOSUS AGAINST EHRLICH’S ASCITES CARCINOMA BEARING MICE

Objective: Our previous research isolated Cucurbitacin B (CuB) and ebenone leucopentaacetate (ELP) from methanolic fruit extract of Cucumis callosus (MFCC). The fruits of C. callosus (Rottl.) Cogn. (Family: Cucurbitaceae) plant have been traditionally used for antioxidant, anti-inflammatory, and antidiabetic actions. The objective of this research was to evaluate in vitro and in vivo anticancer effect of MFCC on Ehrlich Ascites Carcinoma (EAC) cell lines.Methods: In vitro anticancer assay of MFCC and standard drug, 5-fluorouracil (5-FU) was evaluated using Trypan blue and 3-(4, 5-dimethylthiazol-yl)-2, 5-diphenyl tetrazolium bromide methods. In vivo anticancer activity of MFCC and 5-FU was also performed after 24h of EAC cells (2×106cells/ mouse) inoculation based on toxicity study for 9 consecutive days. The activity of the extract was assessed by the study of tumor volume, tumor weight, viable and non-viable cell count, hematological parameters, and biochemical estimations.Results: The MFCC showed the direct antitumor effect on EAC cells in a dose-dependent manner with an IG50 value of 0.61 mg/ml. Furthermore, MFCC (350 mg/kg) exhibited significant (p<0.01) decrease in tumor volume, tumor weight, and viable cell count of EAC-treated mice. Hematological profile, biochemical estimation assay significantly (p<0.01) reverted to normal level in MFCC, and 5-FU treated mice.Conclusion: The anticancer activity of fruits of C callosus is may be either due to the presence of CuB or/and ELP as phytoconstituent and the activity is comparable to standard drug 5-FU.

EVALUATION OF ANTICANCER ACTIVITY OF ETHANOLIC EXTRACT OF CYPERUS KYLLINGIA ENDL. IN EHRLICH ASCITES CARCINOMA-INDUCED SWISS ALBINO MICE

Objective: The purpose of the study was to evaluate the antitumor and antioxidant status of ethanolic extract of Cyperus kyllingia Endl. on Ehrlich ascites carcinoma (EAC)-treated mice.Methods: The determination of in vivo antitumor activity was performed using EAC cells inoculated mice groups (n=12). The groups were treated for 9 consecutive days with ethanolic extract of C. kyllingia (EECK) at the doses of 20 and 40 mg/kg b.w., respectively. After 24 h of the last dose, half of the mice were sacrificed and the rest were kept alive for assessment of increase in life span. The antitumor potential of EECK was assessed by evaluating tumor volume, viable and non-viable tumor cell count, tumor weight, hematological parameters, and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver tissue enzymes.Results: EECK showed direct cytotoxicity on EAC cell line in a dose-dependent manner. EECK exhibited significant (p<0.05) decrease in the tumor volume, viable cell count, tumor weight, and elevated the life span of EAC tumor-bearing mice. The hematological profile, biochemical estimations, and tissue antioxidant assay were reverted to normal level in EECK-treated mice.Conclusion: Experimental results revealed that EECK possesses potent antitumor and antioxidant properties. Further, research is going on to find out the active principle(s) of EECK for better understanding of mechanism of its antitumor and antioxidant activity.

Indian toad (Bufo melanostictus, Schneider) skin extract induces apoptosis and shows cytotoxic effect on Ehrlich ascites carcinoma (EAC) cells

Indian toad (Bufo melanostictus) skin extract (TSE) was evaluated for cytotoxic and apoptogenic activities on Ehrlich ascites carcinoma (EAC) cells of EAC bearing Swiss albino male mice. LD50 of TSE was found to be 400 mg kg-1, (i.v.) and 750 mg kg-1, (i.p.) in mice. EAC cells (1-2 ´ 105 / mouse) were inoculated (i.p.) into mice (20.6 ± 0.14 gm) and the status of EAC cell proliferation and viability were studied in control and TSE treated groups. TSE (10, 20, 30 mg kg-1 d-1, i.p. for 10 d) significantly inhibit EAC cell growth in dose dependent manner. TSE (50, 100 mg kg-1 d-1, i.p. for 1 d) significantly reduced the viability of EAC cells and decreased the MTT values compared to control cells. TSE induced DNA breakage was reflected in DNA ladder and single cell gel electrophoresis (comet assay). TSE significantly (P<0.001) increased the number tailed cells and length-width ratio of DNA mass in EAC cells as compared to control. Fluorescent microscopy of TSE treated cells showed significant increase in number of early and late apoptotic cells compared to the control EAC cells. Apoptotic index of TSE treated cells was significantly (P<0.001) higher than that of the control cells. Changes in serum LDH, β2-microglobulin in TSE treated EAC mice and our earlier studies indicated the involvement of immunomodulation which may indirectly be associated with the anticancer activity of TSE.
 Keywords: Toad skin extract; Bufo melanostictus; Ehrlich ascites carcinoma; Cytotoxic agent;

Purification, characterization and immunogenicity assessment of glutaminase free L-asparaginase from Streptomyces brollosae NEAE-115

BackgroundL-asparaginase is a potential therapeutic enzyme widely used in the chemotherapy protocols of pediatric and adult patients with acute lymphoblastic leukemia. However, its use has been limited by a high rate of hypersensitivity in the long-term used. Hence, there is a continuing need to search for other L-asparaginase sources capable of producing an enzyme with less adverse effects.MethodsProduction of extracellular L-asparaginase by Streptomyces brollosae NEAE-115 was carried out using submerged fermentation. L-asparaginase was purified by ammonium sulphate precipitation and pure enzyme was reached using ion-exchange chromatography, followed by enzyme characterization. Anticancer activity towards Ehrlich Ascites Carcinoma (EAC) cells was investigated in female Swiss albino mice by determination of tumor size and the degree of tumor growth inhibition. The levels of anti-L-asparaginase IgG antibodies in mice sera were measured using ELISA method.ResultsThe purified L-asparaginase showed a total activity of 795.152 with specific activity of 76.671 U/mg protein and 7.835 − purification fold. The enzyme purity was confirmed by using SDS–PAGE separation which revealed only one distinctive band with a molecular weight of 67 KDa. The enzyme showed maximum activity at pH 8.5, optimum temperature of 37 °C, incubation time of 50 min and optimum substrate concentration of 7 mM. A Michaelis-Menten constant analysis showed a Km value of 2.139 × 10− 3 M with L-asparagine as substrate and Vmax of 152.6 UmL− 1 min− 1. The half-life time (T1/2) was 65.02 min at 50°С, while being 62.65 min at 60°С. Furthermore, mice treated with Streptomyces brollosae NEAE-115 L-asparaginase showed higher cytotoxic effect (79% tumor growth inhibition) when compared to commercial L-asparaginase group (67% tumor growth inhibition).ConclusionsThe study reveals the excellent property of this enzyme which makes it highly valuable for development of chemotherapeutic drug.

Overexpressed CYP450 mediated apoptosis evaluates cytotoxicity and teratotoxicity of Cucumis callosus

Fruits of Cucumis callosus (Rottl.) Cogn. (Family: Cucurbitaceae) plant, are commonly known as “bitter cucumber” (English) and “Kachri” (Hindi) in India and have been traditionally used for antioxidant, rich source of vitamin C, antidiabetic and anticancer actions. Tribal peoples of Odissa and West-Bengal are using these fruits during worship and as a vegetable. In vitro cytotoxicity of methanolic seed extract of C. callosus (MSCC) at different concentrations (25, 50, 100, 200, 400) µg/ml and methanolic pericarp extract of C. callosus (MPCC) at (30, 60, 120, 240, 360) µg/ml on Ehrlich Ascites Carcinoma (EAC) cell line, has been evaluated by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and Trypan blue dye exclusion assay for a period of 3 h treatment. Acute toxicity and in vivo teratotoxicity of both extracts were also evaluated using the Zebrafish embryo developmental assay. The MSCC and MPCC showed the direct cytotoxic effect on EAC cells in a dose-dependent manner with IG50 value 273.17 and 235.08 µg/ml respectively. The MPCC in 240 and 360 µg/ml showed a strong teratotoxic effect on Zebrafish embryo in a dose-dependent manner. The cytotoxicity and teratotoxicity of MPCC were due to overexpressed CYP450 mediated apoptosis in the tissue.

Synthesis, characterization, and antitumor activity of some novel S-functionalized benzo[d]thiazole-2-thiol derivatives; regioselective coupling to the –SH group

Abstract Several 2-substituted sulfanyl benzo[d]thiazoles were regioselectively synthesized by the reaction of benzo[d]thiazole-2-thiol (1a) with a variety of reagents under different basic conditions. Some 2-(2,3-disubstituted propyl sulfanyl)benzo[d]thiazoles were obtained from 2-(allylthio)benzo[d]thiazole, which was prepared by the allylation of 1a with allyl bromide in the presence of sodium hydride in dry N,N-dimethylformamide. Reaction of 1a with various pyrazolyl-quinoxaline derivatives was also investigated. Better yields and shorter reaction time were achieved for the synthesis of some derivatives by using ultrasound irradiation. The structural elucidation of all compounds was based on both analytical and spectroscopic data. The newly synthesized compounds were tested in vitro for their antitumor activity against Ehrlich ascites carcinoma (EAC) cells grown in albino mice. Doxorubicin was used as a standard antitumor antibiotic, and some compounds showed half maximal inhibitory concentration (IC50) in the range 40–68 μg mL−1.

Silymarin nanoformulation as potential anticancer agent in experimental Ehrlich ascites carcinoma-bearing animals.

This study aimed to evaluate, for the first time the potential use of a safe biocompatible nanoformulation of silymarin (SM) as antitumor agent and to provide its mechanism of action compared with native SM. SM was loaded into pluronic nanomicelles and Ehrlich ascites carcinoma-tumor-bearing mice were used as experimental model. Biochemical parameters including SOD, CAT and GSH, lipid peroxidation biomarkers (MDA), histopathological, ultrastructural and immunohistochemical studies were applied on the Ehrlich ascites carcinoma cells. Furthermore, the cell cycle as well as caspase-3 were examined. Nanoformulated SM (SMnp) destroyed tumors via increasing SOD, CAT and GSH concomitant with decreasing MDA. Moreover, SMnp-induced apoptosis through decreasing Ki-67 and Bcl2 expression, along with the activation of caspase-3, leads to inhibition of proliferation and the arrest of ceel cycle progression at the G1/S phase. Electron microscopy studies presented the superiority of SMnp over native SM in causing mitochondrial and nuclear degeneration in cancer cells.

Antitumor effect of a crude protein-bound polysaccharide substance extracted from Volvariella speciosa

Mushroom polysaccharides, as the main active ingredient in the mushroom, inhibit cancer cells by activating host immune system. These special properties along with minimal side effects make mushroom polysaccharides as novel anticancer therapies. The present study involved the investigation of polysaccharides from fruit bodies of Volvariella speciosa on growth of Ehrlich ascites carcinoma (EAC) cell lines. In a pilot study two modes of treatment were used, prophylactically and treatment after tumor injection. The prophylactic treatment doesn't rule out its role in the antitumor effect by these PS. However, the other mode of treatment showed better results. A significant reduction in tumor volumes in tumor bearing mice treated with PS was accompanied with a significant reduction in both liver DNA and RNA in addition to an increase in the total lipids and proteins. A significant increase in SOD together with decrease in MDA was noticed. A highly significant decrease in Alk-Ph, ALT and AST and an elevation in albumin after treatment the groups of tumor-bearing mice with the PS substance compared with those saline-treated tumor-bearing mice. The haematological parameters were found to be altered toward normal values. An elevation of IFN-γ, IL-2, IL-12 and reduction in IL-10 were recorded. In the acute toxicity tests, no mortality or sign of induced modifications in the biochemical parameters were observed after PS treatment. The IR has characteristic bands attributed to (1−3) β glucan linkage with a protein moiety. These polysaccharides should be conducted in the future to achieve their use in different potential applications.

In vivo anticancer activities of Ni (II)-Benzoin thiosemicarbazone complex [Ni(BTSC)2] against ehrlich ascites carcinoma cells

Cancer is a class of diseases in which a group of cells display uncontrolled growth, invasion and sometimes metastasis. In order to find out a new anticancer drug, Ni(II) complex with benzoin thiosemicarbazon was synthesized and characterized. Anticancer activities of Ni(BTSC)2 2 2 has been studied against Ehrlich Ascites Carcinoma (EAC) cells in Swiss albino mice by monitoring tumor cell growth inhibition, tumor weight measurement, survival time of tumor bearing Swiss albino mice. Hematological parameters were also studied in both normal and EAC bearing treated mice. The results were compared with those obtained with a standard anticancer drug bleomycin and the compound was found to possess pronounced anticancer effect. Maximum cell growth inhibition was found to be 77.15% after treatment with Ni(BTSC)2 at the dose of 8 mg/kg (i.p). About 69.56% enhancement of life span was found at 8 mg/kg (i.p).With the same dose Ni(BTSC)2 reduced the tumor weight by 52.17% at day 20. The hematological parameters (WBC, RBC, hemoglobin content and differential counts) were found to be significantly changed as compared to those of the normal mice. These parameters restored more or less towards normal when treated with the test compound.J. bio-sci. 23: 77-88, 2015

Bis(thiosemicarbazone)copper(I) Complexes as Prospective Therapeutic Agents: Interaction with DNA/BSA Molecules, and In Vitro and In Vivo Anti‐Proliferative Activities

AbstractA series of six new bis(thiosemicarbazone)copper(I) complexes of the type [Cu(L1–6)2Cl] (1−6) were synthesized and characterized. The complexes adopted trigonal planar ′Y′ shaped geometry coordinating through two thione sulphur atoms of two ligand molecules and one chloride ion. All the complexes intercalatively bind with calf thymus DNA (CT−DNA) as evidenced by spectral and molecular docking studies. The absorption and emission spectral techniques confirmed the strong interaction of the complexes with BSA via static quenching mode. The complexes efficiently cleave pBR322 DNA via hydrolytic pathway, and significantly interact with epidermal growth factor receptor. All the complexes were assessed for their anti‐proliferative activity, in which the complexes 2, 3 and 4 containing methyl, methoxy and hydroxyl groups, respectively, showed significant activity. The complexes induce apoptosis in EAC cells as evidenced by acridine orange (AO)/ethidium bromide (EB), Hoechst 33258 and propidium iodide (PI) staining methods, and cell cycle analysis. Cellular uptake studies revealed the ability of the complexes to go into the cytoplasm and accumulation in the cell nuclei. The complexes are involved in the generation of reactive oxygen species (ROS), mitochondrial mediated and caspase‐dependent apoptosis. Further, using a female Swiss albino mice model, we found that the complexes 2 and 3 inhibited Ehrlich ascites carcinoma (EAC) tumour cell growth in vivo.

EVALUATION OF HEAMAGGLUTINATION AND ANTI-CANCER POTENTIAL FROM INDIAN DIETARY PLANTS

Objective: To evaluate the agglutination and anti-cancer activity of different dietary plants, commonly used in Indian dietary system for its therapeutic applications.Methods: Sap/phloem exudates from different dietary plants were collected in phosphate buffer saline (PBS) was evaluated for lectin activity by using haemagglutination method in serial dilution manner. Anticancer activity of the different samples was evaluated against Ehrlich ascites carcinoma (EAC) cells by using trypan blue exclusion method.Results: Samples belongs to Cucurbitaceae family showed promising lectin activity among test samples. Praecitrullus fistulosus and Cucumis prophetarum give 256HU/mg whereas Cucumis dipsauses gives 128HU/mg activity, whereas Abelmoschus esculentus (16HU) which gives low lectin activity. Praecitrullus fistulosus shows anticancer activity 67.38% inhibition at 200µg concentration followed by Cucumis prophetum of 56.36% at 200µg concentration against Ehrlich ascites carcinoma (EAC) cells.Conclusion: The present study demonstrated that dietary lectin having a potential role in the biological field. High lectin activity demonstrates the anticancer effect in Ehrlich ascites carcinoma (EAC) model system, in vitro. Further study needs to isolate and evaluate biologically active lectin molecule in order to demonstrate the anticancer effect.

Growth Inhibition and Apoptosis of Ehrlich Ascites Carcinoma Cells by Methanol Extract from the Calyx of Hibiscus Sabdariffa Linn

Objectives: This study focused on the antioxidant and anticancer activities of methanolic extract of Hibiscus sabdariffa calyx. Methods: In vitro methods were used to determine the different types of phytochemical content and antioxidant activity of methanolic extract of Hibiscus sabdariffa calyx as well as its cytotoxic effect against Ehrlich ascites carcinoma cells. In vivo, the antineoplastic effect of methanolic extract of Hibiscus sabdariffa calyx against Ehrlich ascites carcinoma was also evaluated by determining the viable tumor cell count, survival time, body weight gain, and hematological profi les of experimental mice along with observing morphological changes of Ehrlich ascites carcinoma cells by fl uorescence microscopy and determining the expression of p53 gene in Ehrlich ascites carcinoma cell assayed by reverse transcription-polymerase chain reaction. Chemical composition of methanolic extract of Hibiscus sabdariffa calyx was analyzed by gas chromatography–mass spectrometry. Results: Flavonoid rich methanolic extract of Hibiscus sabdariffa calyx had showed remarkable antioxidant activity and in in vitro assay, methanolic extract of Hibiscus sabdariffa calyx had potent inhibitory effect against Ehrlich ascites carcinoma cells with a half maximal inhibitory concentration of 28.16 µg/mL. Apoptotic morphological changes and increased expression of p53 gene in Ehrlich ascites carcinoma cells derived from methanolic extract of Hibiscus sabdariffa calyx-treated (5 and 10 mg/kg/day) mice were also observed. Moreover, chemical constituents identifi ed by gas chromatography–mass spectrometry analyses were likely related to this activity. Conclusion: Methanolic extract of Hibiscus sabdariffa calyx has promising antioxidant and antineoplastic potential and can be considered as a probable new source for antitumor agent.

In vivo antitumor activity of by-products of Passiflora edulis f. flavicarpa Deg. Rich in medium and long chain fatty acids evaluated through oxidative stress markers, cell cycle arrest and apoptosis induction

Antiinflammatory and antitumor activity has been reported in Passiflora edulis (yellow passion fruit) nevertheless the intrinsic mechanisms of action are not fully elucidated. The present study aimeds to perform a comparison between the antitumor activity involving the crude extract (HCE) and the supercritical fluid extract with ethanol as co-solvent (SFEtOH) from P. edulis f. flavicarpa Deg. The in vitro cytotoxicity was evaluated in MCF-7 cells, while the in vivo antitumor activity was assessed in male Balb/c mice inoculated with Ehrlich carcinoma cells. SFEtOH exhibited higher antitumor activity compared to HCE. Wherein, SFEtOH showed an EC50 of 264.6 μg/mL against MCF-7 cells as well as an increased inhibition of tumor growth of 48.5% (p < 0.001) in male Balb/c mice, thereby promoting an increased mice lifespan to approximately 42%. Moreover, SFEtOH caused lipid (p < 0.001) and protein (p < 0.001) oxidation by increasing glutathione redox cycle activity while decreased the thioredoxin reductase activity (p < 0.001). SFEtOH also induced oxidative DNA damage in Ehrlich ascites carcinoma (EAC) cells leading to G2/M cycle arrest and has increased apoptotic cells up to 48.2%. These data suggest that the probable mechanisms of antitumor effect are associated to the lipid, protein and DNA damage, leading to cell cycle arrest and triggering apoptosis via mitochondrial pathway, should be probable due to the presence of medium and long chain fatty acids such as lauric acid.