scholarly journals EVALUATION OF IN VIVO ANTICANCER AND IMMUNOSTIMULATORY ACTIVITY OF FLOWERS OF MIMOSA PUDICA LINN. (FABACEAE)

Author(s):  
Debaprotim Dasgupta ◽  
Suvakanta Dash

Objective: To investigate the in vivo anticancer and immunostimulatory activity of dichloromethane (DCM) extract of flowers of Mimosa pudica and its isolated compound 11β hydroxy-3 methoxy 1,2 dehydro crinane.Methods: The anticancer activity was performed on Ehrlich ascites carcinoma (EAC) cell line in Swiss albino mice. The activity was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological, and histopathological parameters of EAC-bearing animals. The immunostimulatory activity was performed through carbon clearance, delayed type hypersensitivity (DTH), neutrophil adhesion and humoral antibody (HA) titer methods.Results: At the dose of 500 and 1000 mg/kg/day p.o for the extracts and 2.5 mg/kg/day p.o. for the isolated compound, significantly decrease the tumor volume (3.46±0.135 ml, 2.25±0.153 ml, and 1.84±0.012), increased the life span (59.32%, 76.39%, and 82.43%) and significantly (p<0.05) decreased tumor weight as compared with control. Hematological profiles were found to be nearly normal level in extract treated mice compared with tumor bearing control mice. The immunostimulatory activity was also found to be effective in the above dosage regimen. The results revealed that animals treated with above doses show a significant increase in the rate of carbon clearance from blood, increase in HA titer value, increase in neutrophil adhesion and significant (p<0.05) increase in mean paw edema in DTH reactions in dose-dependent manner.Conclusion: The results demonstrated that the extract is possessing dose-dependent anticancer activity and immunostimulatory activity attributed to the presence of crinane alkaloid.

Author(s):  
Siva Prasad Panda ◽  
Rajsekhar Reddy A ◽  
Uttam Prasad Panigrahy

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.


Author(s):  
Prameela Rani A ◽  
Agarjuna Babu E ◽  
Prem Madhur S ◽  
Ravi Chandra Sekhara Reddy D ◽  
Phani Kumar K

 Objective: The objective of the study was to investigate the anticancer activity of the ethanolic extract of Parkinsonia aculeata (EEPA) leaves. Methods: Anticancer activity of P. aculeata (EEPA) of leaf extract was evaluated in Swiss albino mice against Ehrlich ascites carcinoma (EAC) cell line at the doses of 200 and 400 mg/kg body weight orally. The extracts were administered for 14 consecutive days. 24 h of the last dose and 18 h of fasting, the mice were sacrificed, and the anticancer effect of EEPA was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters, and biochemical parameters of EAC bearing mice.Results: P. aculeata extracts showed a significant decrease in (p<0.01) tumor volume, viable cell count, tumor weight, and elevated the life span of EAC bearing mice. Hematological profile such as red blood cell, hemoglobin count reverted to normal level in EEPA treated mice. The extracts significantly (p<0.05) decreased the levels of lipid peroxidation and significantly (p<0.05) increased the levels of reduced glutathione, superoxide dismutase and catalase.Conclusion: The results showed that the EEPA was effective in inhibiting the tumor growth in ascitic models and that is comparable to 5-fluorouracil. 


2020 ◽  
Vol 10 (4) ◽  
pp. 395-399
Author(s):  
Ajay M. Chowdari ◽  
D. Giles

Background: Ziziphus jujuba mill was commonly used for its anti-inflammatory activity in traditional system of medicine. Objective: The purpose of this study was to examine the isolates of methanolic extract from the fruits of Ziziphus jujuba Mill for its antiulcer, anti-inflammatory, and anticancer activity. Methods: Methanolic extracts of Ziziphus jujuba Mill were subjected to chromatography and eluted using ethyl acetate: methanol mixture and investigated for its structural features using IR, 1H NMR, 13C NMR and mass spectral data. The isolated compound was evaluated for its in vitro COX-2 inhibition studies, cytotoxicity studies, in vivo anti-inflammatory, antiulcer and anticancer activity. Results: The spectral data revealed that the backbone of the isolate was 3-O-α-L-rhamnopyranosyl- (1→6)-β-D-glucopyranosyl jujubogenin-20-O-(2,3,4-O-triacetyl)-α-L-rhamnopyranoside. The isolated compound showed a significant reduction in inflammation and edema. Moderate anticancer activity was also observed for the isolate. Conclusion: It was concluded that the isolated saponin possesses moderate antiulcer, antiinflammatory, and anticancer activity which could help in the identification of leads for the treatment of cancer-related inflammation.


Author(s):  
Sarjan H. N. ◽  
Yajurvedi H. N.

Objective: To find out whether an isolated compound (IC) from the ethanolic extract of roots of ashwagandha prevents stress-induced hyperglycemia by direct interference with the action of increased concentration of corticosterone on hepatocytes or by preventing hyper-secretion of corticosterone or both.Methods: A group of rats served as controls, and those in another group were subjected to restraint (1 h) and forced swimming exercise (15 min), after a gap of 4 h daily for 4 w. The third group of rats received orally IC (5 mg/kg bw/rat) 1 h prior to exposure to stressors. After the last treatment period, a blood sample was collected and serum was separated for the estimation of corticosterone and glucose. In in vitro experiment, hepatocytes were treated with different concentrations of corticosterone (100, 200, 300, 400 and 500 ng/ml). In another set of experiment, hepatocytes were treated with different doses of IC (1, 10, 100, 1000 and 10 000 μg/ml of medium) along with corticosterone (400ng/ml). The concentration of glucose and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined after the treatment.Results: Stress exposure caused a significant increase in serum concentration of corticosterone and glucose whereas, administration of IC did not result in similar changes. Further, treatment of corticosterone in in vitro significantly increased the activities of PEPCK and G6Pase and concentration of glucose in a dose-dependent manner in hepatocytes. However, treatment with IC did not interfere with the corticosterone-induced an increase in the activities of PEPCK and G6Pase as well as the concentration of glucose in hepatocytes.Conclusion: The in vivo and in vitro results put together reveal that IC does not directly interfere with the action of corticosterone on hepatocytes. However, it prevents stress-induced hyperglycemia by suppressing hyper-secretion of corticosterone. 


Author(s):  
Subeer Roy ◽  
Diksha Kumari ◽  
Mainak Chakraborty ◽  
Pallab Kanti Haldar

Objective: Methanol extract of Calamus rotang (MECR) root was appraised as a spotlight for the candidate of anticancer activity through the vehicle (Ehrlich Ascites Carcinoma) on Swiss albino mice.Methods: In vitro cytotoxicity assay has been accessed by trypan blue and MTT assay. In vivo anticancer activity was done using EAC cells (2 × 106) where in each groups mice were 6. After treatment with MECR at the lower dose of 200 and higher dose of 400 mg/kg respectively for 9 d, half of the mice of each group were sacrificed and the rest were kept to check prolongation of life span. The anticancer potential of MECR was evaluated by tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters, biochemical estimations and Furthermore, tissue antioxidant parameters. Besides, solid tumor activity was also inspected.Results: In MECR treated groups (200 and 400 mg/kg) tumor volume, packed cell volume and viable cell count was significantly lessened as compared to that of the EAC control group. Life span, most reliable criteria for anticancer study, increased quite surprisingly by 50% and 100% in a dose dependant manner while compared to EAC control group. The hematological, biochemical and liver tissue antioxidant parameter are significantly (p<0.05) restored along with solid tumor case study (solid tumor volume) towards the normal level after treatment with MECR.Conclusion: From the above study it can be inferred that the MECR has impressive anticancer activity in dose dependent way.


2011 ◽  
Vol 365 ◽  
pp. 222-227
Author(s):  
Li Tang ◽  
Li Yu

Recent studies have shown that Genistein can obviously suppress growth of gynecologic carcinoma. In this study we examined whether Genistein and Cisplatin, alone and in combination, exhibited a inhibitory effect on the growth of ovarian carcinoma. SKOV3 cells were treated with 20µM Genistein, 20µM Cisplatin and combination group (G+C) for 24 to 72 hours, antiproliferative effect was tested by MTT method. Apoptosis was evaluated using flow cytometry and transmission electron microscopy. Then the transplanted xenografts were treated with Genistein and Cisplatin, the tumor volume and tumor weight were measured, HE staining were performed for morphologic observation. A time and dose-dependent growth inhibition was observed. When treated the cells with 20µM Genistein, 20µMCisplatin and combination group (G+C), compared with the control group, the growth of cells in different treatment group was inhibited, while the combination of Genistein and Cisplatin showed significant inhibition effect than single agent. When Genistein (0.4mg/kg, s.c.) treated the transplanted xenograft in vivo, the tumor volume and tumor weight decreased, T/C ratio (mean volume of treated group/mean volume of control group) also was reduced compared to untreated group, and extensive necrotic areas in the tumor treated with Genistein and Cisplatin appeared in HE section. A weight loss of nude mice after treatment with Genistein was not significant as compared with the control group. And when treated with Genistein (0.4mg/kg, s.c.) and Cisplatin (4mg/kg, i.v.), it showed a synergistic effect. Genistein and Cisplatin, alone and in combination, suppress cell growth. The combination of Genistein and Cisplatin, as compared to single treated group, caused a synergistic increase in antiproliferative effect on SKOV3 cells. The implication for treatment of ovarian cancer may be combination of Genistein and Cisplatin. Further studies are needed to supply more evidence.


1981 ◽  
Vol 50 (1) ◽  
pp. 329-344
Author(s):  
J.V. Forrester ◽  
J.M. Lackie

The effects of hyaluronate on rabbit neutrophil adhesion were studied using a variety of techniques. Exogenous hyaluronate inhibited neutrophil aggregation under conditions of both turbulent flow and constant shear rate. Hyaluronate also inhibited neutrophil adhesion to glass. Inhibition was dose-dependent above 100 micrograms ml-1 and a minimum molecular weight for hyaluronate of 1 × 10(4) was required. These effects were not simply the result of increased bulk viscosity of the hyaluronate-containing medium, nor did they appear to be mediated by putative cell-surface receptor mechanisms. Instead, physical factors such as hindrance and/or changes in the interfacial free-energy exchange at the cell surface due to the unusual hydrodynamic properties of the hyaluronate molecule were considered to be more important. Since neutrophil migration in vivo occurs through hyaluronate-rich connective tissue matrices, the relevance of these findings for processes such as inflammation and wound healing is clear.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4888-4888
Author(s):  
Li Long ◽  
Xia Tong ◽  
Montesa Patawaran ◽  
Lea Aukerman ◽  
Bahija Jallal ◽  
...  

Abstract CD40 is expressed on most B cell malignancies including multiple myeloma and represents an attractive target for antibody therapy. We have generated a novel, highly potent, fully human antagonistic anti-CD40 monoclonal antibody, CHIR-12.12, using XenoMouse® mice (Abgenix, Inc). The antibody can mediate anti-tumor activity potentially by at least two mechanisms: CHIR-12.12 can block CD40-ligand mediated survival signals and it can lyse tumor cells by antibody-dependent cellular cytotoxicity (ADCC). We have previously reported that CHIR-12.12 mediates stronger killing of CD40- and CD20-expressing lymphoma cells than rituximab by ADCC in vitro and significantly inhibits the growth of both rituximab-responsive and rituximab-resistant human lymphoma xenografts in vivo. In this study, we examined in vitro and in vivo efficacy of CHIR-12.12 against human multiple myeloma. The human MM cell line IM-9, which expresses both CD40 and CD20, the target antigen for CHIR-12.12 and rituximab respectively was used for the study. CHIR-12.12 induced lysis of target tumor cells by ADCC in a dose dependent manner reaching maximum cell lysis at 0.1ug/ml concentration. The maximum specific lysis of IM-9 cells by CHIR-12.12 was greater than the lysis induced by rituximab (64% vs 45 %, n=3, p<0.01). In addition, the EC50 of CHIR-12.12 was on average 5.9 picomolar, which was 10-fold lower than the EC50 of rituximab. Greater ADCC by CHIR-12.12 was not due to higher density of CD40 molecules on the target tumor cells compared to CD20 molecules. IM-9 cells expressed 35590 ±8858 CD40 molecules compared to 93783 ± 2247 CD20 molecules. The in vivo CHIR-12.12 efficacy was then evaluated in IM-9 xenograft model. In an un-staged conditional survival model, where treatment began one day after intravenous inoculation of IM-9 tumor cells, CHIR-12.12 significantly prolonged the survival of tumor-bearing mice in a dose-dependent manner with 60% survival in the 0.1 mg/kg CHIR-12.12 treated group and 80% survival in the 1 and 10 mg/kg groups respectively on day 56 (Log Rank Test: P<0.01 and P<0.001, respectively). All animals in the control IgG1 and bortezomib treated groups were terminated between day 18 and day 26 due to severe disease related to tumor development (i.e., hind limb paralysis and significant body weight loss). In a staged subcutaneous model, where treatment began once the tumor volume was 150–200mm3, CHIR-12.12 administered weekly at 0.1, 1 and 10 mg/kg significantly inhibited tumor growth with a tumor volume reduction of 17% (P>0.05), 34% (P<0.01) and 44% (P<0.001) respectively. Bortezomib, when tested at 0.5 mg/kg twice a week did not inhibit tumor growth. At the maximally tolerated dose (MTD) of 1 mg/kg twice a week, bortezomib inhibited tumor growth by 30% (P<0.01). Taken together, these data demonstrate that the anti-CD40 mAb CHIR-12.12 has potent activity against human multiple myeloma in vitro and xenograft models in vivo.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 771-771
Author(s):  
Anil Prasad ◽  
Ashutosh Shrivastava ◽  
Ramana Reddy ◽  
Amanda M. Gillum ◽  
E. Premkumar Reddy ◽  
...  

Abstract Abstract 771 Mantle cell lymphoma (MCL) is a well-defined subtype of B-cell non-Hodgkin's lymphoma characterized by a t(11;14)(q13;q32) chromosomal translocation, and associated with constitutive over-expression of cyclin D1. MCL generally has poor clinical outcome marked by relapse. There is considerable need for novel and more effective agents against MCL. ON 013105 belongs to the styryl benzylsulfones, a novel family of non-ATP competitive kinase inhibitors with potent antitumor activity. Here, we report that ON 013105 induced cell death in a dose-dependent manner in two well-characterized MCL cell lines, Granta 519 and Z138C. In vitro cell death was preceded by the activation of caspases 3 and 9 and cleavage of PARP, indicating induction of apoptosis. In addition, ON 013105-treated cells exhibited reduced expression of cyclin D1 and c-myc. These effects on expression and apoptosis were not evident in cells treated with ON 013101, an inactive (non-cytotoxic) isomer of ON 013105. Since it is common clinical practice to combine Rituximab (RTX) with chemotherapy regimens in treating CD20+ B cell-lymphoma, we studied ON 013105 combined with rituximab, and found ON 013105-induced apoptosis more efficiently than when employed as a single agent. The combination effect on cell death was synergistic in nature. To further study this activity, we focused on Mcl-1, a member of the anti-apoptotic Bcl-2 family known to inhibit apoptosis induced by cytotoxic stimuli through antagonizing pro-apoptotic Bcl-2 family members. We observed a dramatic decrease in Mcl-1 expression in cells treated with ON 013105 (but not with ON 013101) in combination with RTX, compared to ON 013105 alone. We also evaluated the effects of ON 013105 in combination with Doxorubicin or Vincristine and found that both these compounds also significantly enhanced the cytotoxic effects of ON 013105. In vivo pharmacokinetics studies in a mouse model system revealed that plasma concentrations up to 50 μM could be safely achieved by administering ON 013105 at 100 mg/kg via i.v or i.p routes. Significant levels of ON 013100 (30-40% of the peak levels of ON 013105), an active metabolite, were also detected in the circulation, presumably due to the in vivo dephosphorylation of ON 013105 by phosphatase action. ON 013105 was well tolerated in mice, both as a single agent and when used in combination with rituximab, and there were no systemic toxic effects to the host and no loss in body weight. In vivo efficacy studies in mouse xenograft models employing transplanted MCL cells demonstrated that ON 013105 effectively inhibited tumor growth in a dose-dependent manner. ON 013015 at 25 mg/kg (Q2D) and 75mg/kg (Q7D) induced 46% and 80 % reduction of tumor volume, respectively, compared to controls, over 4 weeks of treatment. Moreover, ON 013105 at 25 mg/kg (Q2D) in a combination regimen with RTX (2.5 mg/kg, Q3D) induced over 85% reduction of tumor volume. Though in vivo efficacy studies of ON013015 (25 mg/kg, Q2D) in combination with Doxorubicin (3.5mg/kg, Q7D) or Vincristine (0.3mg/kg, Q2D) showed drastic decrease in tumor growth in mouse models, this effect was accompanied by severe side effects to the host, including mortality. In sum, ON 013105, alone and in combination with RTX may be a potent therapeutic agent against MCL. A Phase I dose escalation trial of ON 013105 as a single agent is underway in patients with relapsed/refractory lymphoma including MCL. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 245 (15) ◽  
pp. 1385-1394
Author(s):  
Jing Wang ◽  
Yanmin Dong ◽  
Qiuming Li

Retinoblastoma is common primary intraocular malignancy of infants and childhood. Neferine is a major bisbenzylisoquinoline alkaloid derived from the lotus plumule in Nelumbo nucifera. This study evaluated the mitigation role of Neferine on retinoblastoma in vitro and in vivo. Xenotransplantation model was established by injecting WERI-Rb-1 cells subcutaneously. Upon induction of retinoblastoma , mice were intraperitoneally injected with Neferine (0, 0.5, 1, 2 mg/kg) or ethanol every 3 days for 30 days. Tumor weight and tumor volume were measured every three days and compared between four groups. Then, mice were sacrificed and immunohistochemical examination was performed to compare Ki67, VEGF content between groups. WERI-Rb-1 cells were used for in vitro experiments and the anti-angiogenic role of Neferine was assessed by analyzing nodes/HPF number. In WERI-Rb-1 xenotransplantation model, compared with control group, 1 mg/kg Neferine treatment significantly inhibited tumor weight (0.39 ± 0.04 g vs. 0.25 ± 0.03 g, P< 0.05) and tumor volume (2163 ± 165 mm3 vs. 1276 ± 108 mm3, P< 0.05) after 30 days. Compared with ethanol-injected mice, 2 μM Neferine treatment significantly enhanced apoptosis rate (2.1 ± 0.6% vs. 14.6 ± 2.6%, P< 0.05), accompany downregulation of Ki67 (0.09 ± 0.02% vs. 0.01 ± 0.004%, P< 0.05) and VEGF (0.28 ± 0.04% vs. 0.05 ± 0.03%, P< 0.05) expression. Additionally, 2 μM Neferine treatment significantly decreased JC-1 red/green percentage. High-dose Neferine could decrease retinoblastoma angiogenesis in association with a significant inhibition on tumor growth and invasion. These findings suggested that Neferine could be a new treatment or adjuvant against retinoblastoma.


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