Tumor Marker Enzymes Research Articles

Amelioration of diethylnitrosamine (DEN) induced renal oxidative stress and inflammation by Carissa carandas embedded silver nanoparticles in rodents.

Inflammation and oxidative stress are the main factors ascribed with interruption in the process of renal tissue impairment. The toxicity of different types of nitrosamine is well recognized in animals and humans. Administration of the smallest quantities of diethylnitrosamine or dimethylnitrosamine either orally or parenterally results into renal damage. Therapeutic effects of phytofabricated silver nanoparticles of Carissa carandas aqueous extract has been scrutinised in current study for the assessment of renal cancer activity in animal model. Phytofabricated silver nanoparticles were characterized by using different instrumentation. Nephroprotective activity of silver nanoparticles at different doses was evaluated against N-diethylnitrosamine (200 mg/kg b.w., intraperitoneal) in animal model. Serum and renal homogenate were taken to evaluate the renal toxicity markers, oxidative stress, and antioxidant parameter, proinflammatory cytokines and histopathological study. Significant outcomes of silver nanoparticles in dose dependent manner down regulated the elevated serum marker, tumour marker enzymes and histopathology observation of repaired tissue assured the renal cancer activity in animals. In addition, profile of enzymatic and non-enzymatic antioxidant, proinflammatory cytokines and tumour promotion marker also favours the anticancer property of silver nanoparticles. The data of current study reveals silver nanoparticles ameliorates renal oxidative stress and carcinogenesis which was induced by N-diethylnitrosamine and accredited to antioxidant and anticancer activities of phytofabricated nanoparticles by biological approach.

Biocompatible Multifunctional Theranostic Nanoprobe for Imaging and Chemotherapy in Solid‐Tumor‐Bearing Mice

AbstractTheranostic carriers are widely studied as they can be exploited for both imaging and drug delivery. However, although there are reports suggesting their in vitro level imaging and drug release, there is necessity to display the application (drug delivery/bioimaging/toxicity) at an in vivo level, which is a pre‐requisite for clinical use. Herein, we demonstrate targeted in vivo imaging and biodistribution in Swiss Albino mice solid tumor model using PEGylated polymer capsules encapsulating LaVO4 : Tb3+ nanoparticles (concentration of nanoparticles ∼3.4 μM LaVO4/kg body weight). The capsules were further loaded with doxorubicin for drug delivery which shows tumor regression at different time intervals in tumor mice model. We have further investigated the tumor marker enzymes including β‐glucuronidase, myeloperoxidase, lactate dehydrogenase, and alkaline phosphatase which clearly suggest the reversion to near normal levels after treating with doxorubicin‐loaded polymer capsules for 30 days. comet assay shows DNA damage in tumor cells induced by doxorubicin. Histology studies performed in tumor tissue and liver show obliteration of tumor cells after treating with doxorubicin‐loaded PEGylated polymer capsules encapsulating LaVO4 : Tb3+ nanoparticles. It has also been observed that the weight of the spleen which was enlarged in solid‐tumor‐bearing mice is significantly lower in animals treated with drug‐loaded capsules.

Diallyl Sulfide-Mediated Modulation of the Fatty Acid Synthase (FASN) Leads to Cancer Cell Death in BaP-Induced Lung Carcinogenesis in Swiss Mice.

PurposeDiallyl sulfide (DAS), one of the organo-sulfur secondary metabolites in garlic, has been shown to inhibit the proliferation of cancer cells. The present study aimed to evaluate the mechanism of DAS in the prevention of benzo[a]pyrene (BaP)-induced lung cancer in a murine model.Materials and MethodsThe mice were exposed to 50 mg/kg of BaP twice a week for 4 weeks in order to induce lung carcinoma. Pretreatment of mice with DAS (100 mg/kg) was started 2 weeks before BaP exposure and further continued for 21 weeks. The effect of DAS and BaP was evaluated by studying various parameters in the serum and tissues of the treated or untreated BaP-exposed mice.ResultsThe histopathological findings demonstrated that DAS prevented the progression of malignant lung cancer and metastasis in the liver. A significant drop was observed in BaP-induced tumor marker enzymes (ADA, AHH, γ-GT, LDH) in the serum of the mice treated with DAS. Moreover, DAS treatment resulted in the recovery of antioxidant enzymes, SOD and CAT, in BaP-exposed mice. The induction of apoptosis and the destruction of cellular ROS were detected in cancer cells from the mice pre-treated with DAS. The immunohistochemical analysis revealed the up-regulation of fatty acid synthase (FASN) in the lungs and liver tissues of BaP-exposed mice and the treatment with DAS inhibited FASN expression.ConclusionThe findings of the present study indicated that DAS-induced apoptosis is strongly associated with the downregulation of FASN in tumor tissues. To the best of our knowledge, this is the first study that describes the role of FASN in BaP-induced lung carcinogenesis.

Lagerstroemia speciosa (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis.

One of the major etiological factors that account for lung cancer is tobacco use. Benzo(a)pyrene [B(a)P], one of the main constituents of tobacco smoke, has a key role in lung carcinogenesis. The present study was conducted to investigate the cytotoxicity of an aqueous ethanolic extract of Lagerstroemia speciosa (L.) Pers leaves (LLE) on human lung adenocarcinoma cells (A549), as well as its in vivo antitumor effect on a lung tumorigenesis mice model. Our results revealed that LLE possesses cytotoxic activity against the A549 cell line. Mice orally administered B(a)P (50 mg/kg body weight) showed an increase in relative lung weight with subsequent decrease in final body weight. Serum levels of tumor marker enzymes AHH, ADA and LDH and the inflammatory mediator NF-κB increased, while total antioxidant capacity (TAC) decreased. In addition, we observed the increased activity of metalloproteinases (MMP-2 and MMP-12) and levels of the tumor angiogenesis marker VEFG and the lipid peroxidation marker MDA, as well as decreased levels of the non-enzymatic antioxidant GSH and enzymatic antioxidants CAT and GSH-Px in lung tissues. Moreover, B(a)P administration up-regulated the expression of the COX-2 gene, pro-inflammatory cytokines TNF-α and IL-6, and an anti-apoptotic gene Bcl-2, and at the same time down-regulated expression of pro-apoptotic genes BAX and caspase-3 and the p53 gene. Pre- and post-treatment with LLE (250 mg/kg body weight) attenuated all these abnormalities. Histopathological observations verified the protective effect of LLE. Overall, the present data positively confirm the potent antitumor effect of L. speciosa leaves against lung tumorigenesis.

Biopotency of Gynandropsis Gynandra L., against Aflatoxin B1- Induced Rats with Reference to Tumour Marker Enzymes

Gynandropsis gynandra L., has been reported to be useful in treatment of various ailments in the Indian system of medicine. We proposed to investigate the biopotency of G.gynandra extract against aflatoxin B1-induced hepatocellular carcinoma in rats. A significant increase (p<0.001) in the activities of cancer marker enzymes γ-GT, LDH, ALP and 5| -NT in serum, liver and kidney with a significant elevation in the serum transaminases with a concomitant decrease in the liver and kidney transaminases activities in AFB1-induced HCC bearing rats were observed when compared with the normal control rats. Treatment with the drug GGE showed a significant reversal of the activities of all the enzymes both in serum and liver. These results indicate that G. gynandra extract could potentially modulate the cancer marker enzymes and thus could elicit suppressive activity on tumour growth in AFB1-induced male albino rats.

Chemopreventive and anti-breast cancer activity of compounds isolated from leaves of Abrus precatorius L.

The present study focuses on isolation and evaluation of the anti-cancer activity of compounds from the leaves of Abrus precatorius. The bioassay-directed strategy was adopted using chromatographic, gas chromatographic-mass spectrum analysis, nuclear magnetic resonance and X-ray crystallography techniques for purification and characterization of active cytotoxic compounds. Further, MDA-MB-231 breast cancer cell lines and 7,12-dimethylbenz (a) anthracene (DMBA) induced virgin female Sprague Dawley (SD) rats were used for in vitro and in vivo cytotoxicity evaluation. Stigmasterol hemihydrate and 9,12-Octadecadienoic acid (Z,Z)-2-hydroxy-1-(hydroxymethyl)ethyl ester or (β-monolinolein) were the two main cytotoxic constituents of leaf extract of A. precatorius, with an IC50 value of 74.2 and 13.2µg/ml, respectively, in MDA-MB-231 cells. Additionally, the treatment with the stigmasterol and β-monolinolein as a combinatorial drug therapy in DMBA-induced female SD rats led to recovery of body weight, decreased tumor weight and volume, without any toxic side effects. Immunohistochemical examination showed extensive cell death and low proliferation in the treated tumor tissues that was confirmed by results from H and E staining, TUNEL assay and Ki-67 index as compared to control animal group. The reversion of glycoprotein, lysosomal and tumor marker enzyme levels back to near-normal levels after treatment with the plant compounds clearly demonstrated the reduction of tumor burden in these animals. This is the first report on isolation and characterization of the two active cytotoxic components from leaves of A. precatorius. Additionally, the profound cytotoxic and tumor-suppressive effect of these two compounds as a combinatorial therapy provide an alternative option for breast cancer treatment.

CHEMO PREVENTIVE EFFECT OF PIPERINE IN N-NITROSODIETHYLAMINEINDUCED AND PHENOBARBITAL PROMOTED EXPERIMENTAL RAT HEPATOCELLULAR CARCINOMA

Every year, almost 5, 00,000 new patients are diagnosed with hepatocellular carcinoma (HCC), primary malignancy of the liver that is associated with poor prognosis. In recent years, development of efficient anti-cancer agents from natural sources has become a major focus of researchers. The present study was designed to investigate the preventive and therapeutic effects of piperine against DEN induced HCC in male wistar rats. Twenty four rats were divided into four groups (n=6). Group I serves as Control, Group II were induced with HCC by DEN (200mg/kg b.wt) followed by phenobarbital (0.05 % w/V), Group III received same as Group II and followed by piperine (50mg/kg b.wt) and Group IV received piperine alone at a dose of 50mg/kg b.wt, up to 16 successive weeks. Results indicated that there is significant increase in relative liver weight (P<0.001) and liver marker enzymes (SGOT, SGPT, ACP, ALP, LDH, gGT, TBIL, Total protein, DNA at P<0.001), tumor marker enzymes (AFP, CEA at P<0.001). also, significant abnormalities were observed in membrane bound enzymes (Ca2+, Na+/K+, Mg2+ ATP age at P<0.001) and electrolytes (Na+, K+ , Ca2+, Mg2+ at P<0.001), whereas the above said alterations were significantly restored in piperine treated groups compared with DEN treated group. The histopathological changes of liver were compared with respective control groups. These findings suggest that piperine can be used as an adjunct to conventional chemo preventive agent, which may provide a novel therapeutic approach to serve as promising agent for treatment of hepatocellular carcinoma.

Carvacrol modulates instability of xenobiotic metabolizing enzymes and downregulates the expressions of PCNA, MMP-2, and MMP-9 during diethylnitrosamine-induced hepatocarcinogenesis in rats.

Hepatocellular carcinoma is the fifth most common malignant tumor in the world, both in terms of incidence and mortality in Asian and Western countries. There are currently limited therapeutic regimens available for effective treatment of this cancer. Carvacrol is a predominant monoterpenoic phenol believed to impede cancer promotion and progression. The present study was conducted to decipher the role of carvacrol during diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male wistar albino rats. Carvacrol (15mg/kg body weight) suppressed the elevation of serum tumor marker enzymes, carcinoembryonic antigen, and α-feto protein induced by DEN. The activities of phase I enzymes increased markedly during DEN induction, but was found to be significantly lowered upon carvacrol treatment. On the contrary, the phase II enzymes decreased in DEN-administered animals, which was improved normalcy upon carvacrol-treated animals. DEN-administered animals showed increased mast cell counts, argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen, and matrix metalloproteinases (MMPs-2/9), whereas carvacrol supplementation considerably suppressed all the above abnormalities. The results suggest that the carvacrol exhibited the potential anticancer activity by inhibiting cell proliferation and preventing metastasis in DEN-induced hepatocellular carcinogenesis.

Design and Synthesis of a Peptidyl-FRET Substrate for Tumor Marker Enzyme human Matrix Metalloprotease-2 (hMMP-2)

Matrix metalloproteases (MMPs) in particular MMP-2, have been associated with several pathological conditions such as ovarian, urothelial, cutaneous, gastric, breast, and cervical cancers, etc. Successful treatment of these pathological conditions requires sensitive, reliable, quick and effective diagnostic tools such as fluorescence resonance energy transfer (FRET) based assays in early stage of the disease. A peptidyl-FRET substrate having seven amino acid residues (PLGLKAR) with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher group has been synthesized using solid-phase fluorenylmethoxycarbonyl (Fmoc) peptide chemistry. The newly designed substrate is stable and shows a Km value of 15 μM for hMMP-2. This Km value is the lowest compared with all other known hMMP-2 substrates having Mca/Dnp. Validation of the new FRET substrate in presence/absence of scorpion venom chlorotoxin, a known hMMP-2 inhibitor, shows an increase in detection efficiency of 6,250 times as compared to commonly used gelatin zymography. The new FRET substrate is much more cost effective and can be used for high throughput screening of hMMP-2 inhibitors in the laboratory for research and diagnostic purposes.

In vitro and in vivo studies on antitumor effects of gossypol on human stomach adenocarcinoma (AGS) cell line and MNNG induced experimental gastric cancer

The present study has evaluated the chemopreventive effects of gossypol on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and on human gastric adenocarcinoma (AGS) cell line. Gossypol, C30H30O8, is a polyphenolic compound that has anti proliferative effect and induces apoptosis in various cancer cells. The aim of this work was to delineate in vivo and in vitro anti-initiating mechanisms of orally administered gossypol in target (stomach) tissues and in human gastric adenocarcinoma (AGS) cell line. In vitro results prove that gossypol has potent cytotoxic effect and inhibit the proliferation of adenocarcinoma (AGS) cell line. In vivo results prove gossypol to be successful in prolonging the survival of MNNG induced cancer bearing animals and in delaying the onset of tumor in animals administrated with gossypol and MNNG simultaneously. Examination of the target (stomach) tissues in sacrificed experimental animals shows that administration of gossypol significantly reduces the level of tumor marker enzyme (carcino embryonic antigen) and pepsin. The level of Nucleic acid contents (DNA and RNA) significantly reduces, and the membrane damage of glycoprotein subsides, in the target tissues of cancer bearing animals, with the administration of gossypol. These data suggest that gossypol may create a beneficial effect in patients with gastric cancer.

Chemopreventive effect of bacoside A on N-nitrosodiethylamine-induced hepatocarcinogenesis in rats

Chemoprevention is an effective approach to control hepatocarcinogenesis. Bacoside A, the active constituent of Bacopa monniera Linn., is anticipated to play a role in chemoprevention of liver cancer. In the present study, we investigated the chemopreventive effect of bacoside A against N-nitrosodiethylamine-induced hepatocarcinogenesis in an animal model. Administration of carcinogen showed a significant elevation in the levels of lipid peroxidation, serum tumor marker enzymes and liver injury marker enzymes with subsequent decrease in the levels of both hemolysate and liver antioxidant status. Bacoside A co-treatment maintained the N-nitrosodiethylamine-induced alterations at near normal level. Histopathological and electron microscopic study of the liver tissue also supports the above biochemical observations. From our findings we conclude that bacoside A is effective to prevent DEN-induced hepatocellular carcinoma by quenching lipid peroxidation and enhancing antioxidant status through free radical scavenging mechanism and having potential of protecting endogenous enzymatic and non-enzymatic antioxidant activity.

Cytotoxic effect of achatininH (lectin) from Achatina fulica against a human mammary carcinoma cell line (MCF7)

The hemolymph-derived achatinin(H) (lectin) from Achatina fulica showed a marked cytotoxic effect on MCF7, a human mammary carcinoma cell line. IC(50) values as measured by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay for achatinin(H) ranged from 6 to 10 microg/ml in the MCF7 cells. MCF7 cells showed significant morphological changes leading to cell death. The above cell death was observed after 48 h of treatment with 8 microg/ml when compared to untreated cells. Alterations in the tumor marker enzymes, as well as in antioxidant enzymes, were observed after achatinin(H) treatment. The specificity and purity of the achatinin(H) was confirmed by the Western blot assay. Achatinin(H) binding to MCF7 cells was detected by anti-achatinin(H), and visualization of the achatinin(H) binding sites on confluent MCF7 cells was confirmed by flourescein isothiocyanate conjugated secondary antibody. MCF7-treated cells fluoresced, indicating the presence of achatinin(H) binding sites. Fluorescence-activated cell sorting analysis of the cell cycle showed a significant increase in S-phase in MCF7 cells after 48 h of achatinin(H) treatment. The cells were arrested in G(2)/M phase of the cell cycle after 48 h with significant changes in cell viability. Cellular damage was confirmed by agarose gel electrophoresis with the characteristic appearance of a DNA streak in treated MCF7 cells indicating the ongoing apoptosis.

Anticarcinogenic Effects of Hexaamminecobalt(III) Chloride in Mice Initiated with Diethylnitrosamine

Hexaamminecobalt(III) chloride ([Co(NH3)6]Cl3) was investigated for its antineoplastic role in relation to tumor marker enzymes, drug metabolizing enzymes, oxidative stress-related parameters, and histopathological analysis of liver and lung tissues of mice. Initiation was performed using a single intraperitoneal injection of diethylnitrosamine (DENA) at a carcinogenic dose of 90 mg/kg body weight. The cobalt complex supplementation at a dose of 100 ppm in drinking water was given ad libitum throughout the experimental period of 14 weeks. In comparison to lung, the cobalt complex supplementation was found to reverse DENA-induced biochemical changes more effectively in liver. Histological examination of liver and lung from DENA-initiated and cobalt-complex-supplemented mice showed considerable protection in the case of liver compared to that of lung. The involvement of the [Co(NH3)6]Cl3 in modulating several factors associated with carcinogenesis induced by DENA thus showed its anticarcinogenic potential against chemically induced hepatocarcinogenesis.

The Effects of Quercetin on Antioxidant Status and Tumor Markers in the Lung and Serum of Mice Treated with Benzo(a)pyrene

Chemoprevention has emerged as a very effective preventive measure against carcinogenesis. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on benzo(a)pyrene (B(a)P) induced carcinogenesis. In the present study, the efficacy of quercetin on the level of lipid peroxides, activities of antioxidant enzymes and tumor marker enzymes in B(a)P induced experimental lung carcinogenesis in Swiss albino mice was assessed. In lung cancer bearing animals there was an increase in lung weight, lipid peroxidation and marker enzymes such as aryl hydrocarbon hydroxylase, gamma glutamyl transpeptidase, 5'-nucleotidase, lactate dehydrogenase and adenosine deaminase with subsequent decrease in body weight and antioxidant enzymes-superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, reduced glutathione, vitamin E and vitamin C. Quercetin supplementation (25 mg/kg body weight) attenuated all these alterations, which indicates the anticancer effect that was further confirmed by histopathological analysis. Overall, the above data shows that the anticancer effect of quercetin is more pronounced when used as an chemopreventive agent rather than as a chemotherapeutic agent against B(a)P induced lung carcinogenesis.

Chemopreventive Role of Lycopene and D-arginine in Benzo (a) Pyrene Induced Lung Cancer with Reference to Lipid Peroxidation, Antioxidant System and Tumor Marker Enzymes

Chemopreventive Role of Lycopene and D-arginine in Benzo (a) Pyrene Induced Lung Cancer with Reference to Lipid Peroxidation, Antioxidant System and Tumor Marker Enzymes

Effect of Strobilanthes crispus on the Histology and Tumour Marker Enzymes in Rat Liver During Hepatocarcinogenesis

Effect of Strobilanthes crispus on the Histology and Tumour Marker Enzymes in Rat Liver During Hepatocarcinogenesis

Effect of Strobilanthes crispus on Tumour Marker Enzymes and Glutathione During Chemical Hepatocarcinogenesis in the Rat

Effect of Strobilanthes crispus on Tumour Marker Enzymes and Glutathione During Chemical Hepatocarcinogenesis in the Rat

Effect of cacao liquor extract on tumor marker enzymes during chemical hepatocarcinogenesis in rats.

This study investigated the effect of cacao liquor extract (CLE) on tumor marker enzymes--alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and glutathione reductase (GR) activities--in plasma and/or liver of hepatocarcinogenic rats, which were induced with diethylnitrosamine and 2-acetylaminofluorene. Twenty-nine male Sprague-Dawley rats (weighing 150-330 g) were divided into four groups (n = 6-8): normal control group (N), normal group + CLE (NE), cancer group (C), and cancer group + CLE (CE). Analysis of variance showed significant differences (P<.05) in the specific activities of ALP, GGT, and GST between the C and N groups. However, GR activity for the C group was not significantly different compared with the N group. In the CE group, the specific activities of ALP, GGT, GST, and GR were significantly lower (P<.05) compared with the C group. The findings showed that CLE could lower the activity of tumor marker enzymes of rats during hepatocarcinogenesis. Based on the results obtained, polyphenol compounds present in the cacao liquor, extracted by using ethanol, have the potential in decreasing the severity of hepatocarcinogenesis.

Evaluation of Chemopreventive Potential of Garlic Extract on N-Nitrosodiethylamine-Induced Hepatocarcinoma in Rats

The protective effects of garlic (Allium sativum) were investigated against N -nitrosodiethylamine (NDEA)-induced hepatic tumourigenesis by assessing tumour marker enzymes; gamma glutamate transpeptidase (GGT), glutathione S -transferase (GST), glucose 6-phosphatase (G6Pase), alkaline phosphatase (ALP), 5'-nucleotidase, aspartate (AST) and alanine transaminases (ALT). The changes in the activities of these enzymes is proportional to the extent of malignancy; thus, they were useful to assess the antineoplastic potency of garlic extract. An elevation in the activities of GGT, GST, 5'-nucleotidase, ALP, AST and ALT and reduction in the activity of G6Pase were observed in rats bearing carcinoma. Oral administration of garlic extract normalised the activities of tumour marker enzymes.

Effect of &lt;I&gt;Semecarpus anacardium&lt;/I&gt; Linn. Nut Extract on Experimental Mammary Carcinoma in Sprague–Dawley Rats with Reference to Tumour Marker Enzymes

Plants are rich sources of natural products used in the treatment of diseases. Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. Because of its wide therapeutic utility, Semecarpus anacardium nut milk extract (Serankottai nei) has been tested against experimental mammary carcinoma in rats. Because the activity of tumour marker enzymes is proportional to the extent of malignancy, changes in the activity of these enzymes from the livers and kidneys of experimental rats were used as indices to assess the antineoplastic potency of the drug. A significant reduction in the activity of aspartate and alanine aminotransferases and a sharp increase in that of lactate dehydrogenase, γ-glutamyl transpeptidase, alkaline phosphatase and 5′-nucleotidase were observed in animals with mammary carcinoma. On administration of Semecarpus anacardium nut extract the activity of these enzymes returned almost to normal control levels. No adverse symptoms or significant changes were observed in drug control rats when compared with normal control rats.