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ABSTRACT: ETB receptor agonist, IRL-1620 (or SPI-1620) presently in US Phase 1 clinical trial, has been demonstrated to selectively and transiently increase tumor blood flow. The present study was conducted to determine the effect of IRL-1620 on radiation therapy in tumor bearing mice inoculated with Dalton's Lymphoma Ascites cells. Tumors were allowed to grow for 30 days to a size of 1.10-1.29 cm3 before starting the treatment. The animals with or without IRL-1620 treatment were exposed to radiation (4 Gy/dose) on every alternate day for a total of 5 doses. Tumor volume was determined twice every week till the end of study. Radiation alone did not affect the tumor volume; however, animals treated with IRL-1620 followed by radiation produced a significant (64%) reduction in tumor volume. Survival of mice improved from 0/10 at 56 days after tumor inoculation in vehicle plus radiation group to 6/10 at 70 days in IRL-1620 (9 nmol/kg) plus radiation group. It is concluded that IRL-1620 improves the efficacy of radiation treatment in tumor bearing mice. (These findings have been earlier presented as an abstract ).
Arzneimittel-Forschung 01/2012; 62(1):14-7. · 0.72 Impact Factor
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ABSTRACT: The cytotoxicity and antitumour activity of the isoquinoline alkaloid berberine was studied in-vitro and in-vivo.Berberine was cytotoxic to L929 cells in culture (IC50 40 μg mL−1), and to mice when given as an acute (LD50 50 mg kg−1, i.p) or chronic (LD50 15 mg kg−1 for 10 days, i.p) dose. At a non-toxic concentration berberine dose-dependently inhibited the tumours induced by Dalton's lymphoma ascites tumour cells in mice. Berberine was more active when given intraperitoneally than orally. The simultaneous administration of berberine potentiated the therapeutic effects of radiation, cyclophosphomide and hyperthermia with a decrease in volume of solid tumours in mice.The results indicate the beneficial use of berberine as an adjuvant response modifier in cancer therapy.
Pharmacy and Pharmacology Communications. 02/2010; 5(12):697 - 700.
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ABSTRACT: Effects of Andrographis paniculata extract and its major component, andrographolide, on cell-mediated immune responses in metastatic tumor bearing animals were studied. NK cell mediated target cell lysis was enhanced by the administration of Andrographis paniculata extract (45.0% cell lysis) and andrographolide (40.2% cell lysis) on the 5th day after tumor induction when compared to untreated metastatic tumor bearing animals in which maximum target cell lysis was observed on 11th day (11.4%). Antibody dependent cell-mediated cytotoxicity (ADCC) was also enhanced by treatment with the extract (42.0% cell lysis) and andrographolide (40.2%) in comparison with the untreated case (11.0%). Similarly, the extract (25%) and andrographolide (22%) showed higher ACC activity than the control (14%) and treatment of extract and andrographolide resulted in significant increase in serum IL-2 and TIMP-1 levels. Furthermore, the levels of proinflammatory cytokines such as IL-1ß, IL-6, GM-CSF and TNF-α were effectively reduced by the administration of extract and andrographolide in metastatic tumor bearing animals.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(3):723-9. · 0.66 Impact Factor
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ABSTRACT: The role of abrin, a toxic lectin isolated from seeds of Abrus precatorius Linn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA) cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death.
Evidence-based Complementary and Alternative Medicine - EVID-BASED COMPLEMENT ALTERN. 01/2009; 6(2):233-238.
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ABSTRACT: The formation of new capillaries from existing blood vessels is critical for tumor growth and metastasis. In this study we report that amentoflavone, a biflavonoid from Biophytum sensitivum, could inhibit the process of angiogenesis. Amentoflavone at nontoxic concentrations (0.05-0.2 microg/ml) showed significant inhibition in the proliferation, migration, and tube formation of endothelial cells, which are key events in the process of angiogenesis. In vivo studies in C57BL/6 mice using amentoflavone showed remarkable inhibition (52.9%) of tumor directed capillary formation. Amentoflavone showed inhibitory effect on the production of various endogenous factors such as IL-1beta, IL-6, TNF-alpha, GM-CSF, and VEGF that control the process of angiogenesis. Amentoflavone treatment could increase the production of IL-2 and TIMP-1, which could successfully shift the equilibrium towards an angiostatic condition. The antiangiogenic activity of amentoflavone was supported by its remarkable suppression in sprouting of microvessels from rat aorta. Our results also show that amentoflavone could inhibit the production of VEGF mRNA in B16-F10 cells. These findings indicate that amentoflavone inhibits angiogenesis by disrupting the integrity of endothelial cells and by altering the endogenous factors that are required for the process of neovascularization.
Biochemistry (Moscow) 03/2008; 73(2):209-18. · 1.06 Impact Factor
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ABSTRACT: Modulation of immune responses to alleviate disease has been of interest for a long time. Intraperitoneal administration of Andrographis paniculata extract along with whole body hyperthermia (WBH) was found to enhance the total WBC count in cyclophosphamide (CTX) and radiation treated animals when compared to untreated control animals. Maximum inhibition in the solid tumor development was observed when the CTX and radiation exposed animals were treated with extract in combination with whole-body hyperthermia. Similarly myeloperoxidase activity in tumor tissue from CTX and radiation-treated animals was also significantly inhibited when they were administered with Andrographis paniculata extract along with whole body hyperthermia. Moreover the production of cytokines such as IL-2 and GM-CSF, which was reduced after combined CTX and radiation treatment was significantly increased by the simultaneous treatment of extract and whole body hyperthermia. The elevated level of serum Tumor Necrosis Factor (TNF-alpha) level, after CTX and radiation treatment was also lowered significantly after the administration of extract and simultaneous exposure of whole-body hyperthermia with respect to untreated tumor-bearing animals.
Immunopharmacology and Immunotoxicology 02/2008; 30(1):181-94. · 1.83 Impact Factor
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ABSTRACT: Effect of terpenoids, ursolic acid and glycyrrhizic acid on the cell-mediated immune response was studied in metastatic tumor-bearing C57BL/6 mice. Intraperitoneal administration of ursolic acid and glycyrrhizic acid (50 mumoles/Kg body wt for 5 consecutive days) was found to produce increased natural killer cell activity (NK-activity) in metastatic tumor-bearing animals. In the glycyrrhizic acid- and ursolic acid-treated groups the peak activity was observed on the 4(th) day (60.2% and 43% cell lysis respectively). Whereas in control animals the maximum cell lysis was obtained only on 16(th) day (25% cell lysis). Administration of terpenoids clearly enhanced the antibody dependent cell mediated cytotoxicity (ADCC). In tumor-bearing control animals maximum cell lysis was obtained only on the 16(th) day (20% cell lysis). But in the case of glycyrrhizic acid- and ursolic acid-treated groups, the maximum lysis was obtained on the 12(th) day. and it was 47% and 32.5% cell lysis, respectively. Intraperitoneal administration of these 2 terpenoids was also found to enhance antibody-dependent complement-mediated cytotoxicity (ACC) in metastatic tumor-bearing animals. The elevated level of GM-CSF in tumor-alone treated control animals (37.9 +/- 1.1 pg/ml) was reduced by the treatment with glycyrrhizic acid (20.3 pg/ml) and ursolic acid (22.5 pg/ml). The highly elevated level of IL-6 (370.1 pg/ml) in control animals was also reduced by the treatment of glycyrrhizic acid (313 pg/ml) and ursolic acid (299 pg/ml). The level of IL-2 was enhanced by the treatment with glycyrrhizic acid (37.9 pg/ml) and ursolic acid (35.9) compared to untreated tumor-bearing control animals (24.9 pg/ml).
Immunopharmacology and Immunotoxicology 02/2008; 30(2):243-55. · 1.83 Impact Factor
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Annals of Oncology. 01/2008; 19:31-31.
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ABSTRACT: The role of abrin, a toxic lectin isolated from seeds of Abrus precatorius Linn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA) cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death.
Evidence-based Complementary and Alternative Medicine 12/2007; 6(2):233-8. · 4.77 Impact Factor
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ABSTRACT: The effect of Sulforaphane on the immune system was studied using BALB/c mice. Intraperitoneal administration of five doses of Sulforaphane (500 microg/dose/animal/day) was found to enhance the total WBC count (12,950 cells/mm3) on 9th day. Bone marrow cellularity (23 x 10(6) cells/femur) and number of alpha-esterase positive cells (1346.66/4000 cells) were also increased by the administration of Sulforaphane. Treatment with Sulforaphane along with the antigen, sheep red blood cells (SRBC), produced an enhancement in the circulating antibody titre and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC (315.83 PFC/10(6) spleen cells) was obtained on the 6th day. Administration of Sulforaphane also showed an enhancement in the phagocytic activity of peritoneal macrophages. Moreover administration of Sulforaphane significantly reduced the elevated level of TNF-alpha production by LPS stimulated macrophages. These results indicate the immunomodulatory activity of Sulforaphane.
Phytomedicine 09/2007; 14(7-8):538-45. · 3.27 Impact Factor
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ABSTRACT: Modulation of immune responses is highly relevant in tumor cell destruction. The present study is focused on the effect of Andrographis paniculata extract (APE) and its isolated compound andrographolide (ANDLE) on cell-mediated immune responses in normal and tumor-bearing control animals. Treatment with APE and ANDLE significantly enhanced natural killer cell activity in normal (APE, 46.82% cell lysis; ANDLE, 40.79% cell lysis) and tumor-bearing animals (APE, 48.66% cell lysis; ANDLE, 42.19% cell lysis) on the fifth day, and it was observed earlier than in tumor-bearing control animals (12.89% cell lysis on day 9). Antibody-dependent cellular cytotoxicity was also increased in APE (45.17% cell lysis on day 11) as well as ANDLE (39.92% cell lysis on day 11)-treated normal and tumor-bearing animals (APE, 47.39% cell lysis; ANDLE, 41.48% cell lysis on day 11) compared to untreated tumor-bearing control animals (maximum of 11.76% cell lysis on day 17). An early enhancement of antibody-dependent complement-mediated cytotoxicity was also observed by the administration of APE and ANDLE in normal as well as tumor-bearing animals. APE and ANDLE administration could significantly enhance the mitogen-induced proliferation of splenocyte, thymocyte, and bone marrow cells. Moreover, treatment of APE and ANDLE significantly elevated the production of interleukin-2 and interferon-gamma in normal and Ehrlich ascites carcinoma-bearing animals.
Integrative Cancer Therapies 04/2007; 6(1):66-73. · 2.14 Impact Factor
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ABSTRACT: Inhibition of angiogenesis is currently perceived as one of the promising strategies in the treatment of cancer. In this study we analyzed the antiangiogenic activity of Andrographis paniculata extract (APE) and its major component andrographolide (ANDLE) using both in vitro and in vivo models. Intraperitoneal administration of APE and ANDLE significantly inhibited the B16F-10 melanoma cell line induced capillary formation in C57BL/6 mice. Analysis of serum cytokine profile showed a drastic elevation in the proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha and GM-CSF and the most potent angiogenic factor VEGF in angiogenesis induced animals. Treatment of APE and ANDLE significantly reduced this elevated levels. Moreover, VEGF mRNA level in B16F-10 cell line showed a reduced level of expression in the presence of APE and ANDLE. Serum NO level which was increased in B16F-10 melanoma injected control animals was also found to be significantly lowered by the administration of APE and ANDLE. Antiangiogenic factors such as TIMP-1 and IL-2 level was elevated in APE and ANDLE treated angiogenesis induced animals. In the rat aortic ring assay APE and ANDLE inhibited the microvessel outgrowth at non toxic concentrations. Taken together our results demonstrate that APE and ANDLE inhibit the tumor specific angiogenesis by regulating the production of various pro and antiangiogenic factors such as proinflammatory cytokine, nitric oxide, VEGF, IL-2 and TIMP-1.
International Immunopharmacology 03/2007; 7(2):211-21. · 2.38 Impact Factor
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ABSTRACT: The stimulatory effect of Andrographis paniculata extract and andrographolide on cytotoxic T lymphocyte (CTL) production was determined in BALB/c mice by Winn's neutralization assay using CTL sensitive EL4 thymoma cells as target cell. Extract and andrographolide showed a significant increase in CTL production in both the in vivo and in vitro models. The survival time of EL4 cells alone in animals was only 27.1 days and it was increased to 51.1 and 44.5 days in extract- and andrographolide treated animals with percentage increase in life span (%ILS) of 88.5 and 64.2, respectively. The survival rate of animals administered EL4 cells incubated with alloimmunized spleen cells (effector cells) from normal BALB/c mice was 35.8 (%ILS 32.1). When this group was treated with 10 doses of extract and andrographolide the life span was further increased to 52.1 days (%ILS 92.2 ) and 48.1 days (%ILS 77.4). Survival days of animal carrying EL4 cells incubated with alloimmunized spleen cells (effector cells) from extract and andrographolide treated animals were 55.5 and 50.3 days respectively. When these animals continued with extract and andrographolide treatment for 10 days their life spans were significantly increased to 62 and 53.8 days, respectively. The level of cytokines such as Interlevkin (IL)-2 and Interferon (IFN)-gamma also was enhanced in these animals when they were treated with extract and andrographolide. This study demonstrated that A. paniculata extract and andrographolide stimulate the CTL production through enhanced secretion of IL-2 and IFN-gamma by T cells and thereby inhibit the tumor growth.
Immunopharmacology and Immunotoxicology 02/2007; 29(1):81-93. · 1.83 Impact Factor
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ABSTRACT: Effect of sulforaphane on cell-mediated immune response (CMI) was studied in B16F-10 melanoma-induced metastasis-bearing C57BL/6 mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in metastatic tumor-bearing animals (43.17% cell lysis, on day 5) and the activity was observed earlier than in tumor-bearing control animals (maximum of 9.76% cell lysis, on day 9). Antibody-dependent cellular cytotoxicity also was enhanced significantly in metastatic tumor-bearing animals (41.20% cell lysis on day 9) after sulforaphane administration compared with untreated control tumor-bearing animals (maximum of 12.62% cell lysis on day 15). An early antibody-dependent complement-mediated cytotoxicity also was observed in sulforaphane-treated tumor-bearing animals (26% cell lysis, on day 15). Administration of sulforaphane significantly enhanced the production of IL-2 and IFN-gamma in metastatic tumor-bearing animals. In addition, sulforaphane significantly downregulated the serum levels of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, and GM-CSF during metastasis. These data clearly suggest that sulforaphane effectively inhibited the spread of metastatic tumor cells through the stimulation of CMI, upregulation of IL-2 and IFN-gamma, and downregulation of proinflammatory cytokines IL-1beta, IL-6, TNF-alpha, and GM-CSF.
Immunopharmacology and Immunotoxicology 02/2007; 29(2):173-86. · 1.83 Impact Factor
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ABSTRACT: Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum.
Immunopharmacology and Immunotoxicology 02/2007; 29(3-4):337-50. · 1.83 Impact Factor
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ABSTRACT: The antiangiogenic activity of Piper longum was studied using in vivo as well as in vitro models. In vivo, antiangiogenic activity was studied using B16F-10 melanoma cell-induced capillary formation in C57BL/6 mice. Intraperitoneal administration of the extract (10 mg/dose/animal) significantly inhibited (50.6%) the number of tumor-directed capillaries induced by injecting B16F-10 melanoma cells on the ventral side of C57BL/6 mice. The cytokine profile in the serum of these animals showed a drastically increased level of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, GM-CSF and the direct endothelial cell proliferating agent, VEGF. Administration of the methanolic extract of P. longum could differentially regulate the level of these cytokines. The level of IL-2 and tissue inhibitor of metalloprotease-1 (TIMP-1) was increased significantly when the angiogenesis-induced animals were treated with the extract. The extract of P. longum at non-toxic concentrations (10 microg/ml, 5 microg/ml, 1 microg/ml) inhibited the VEGF-induced vessel sprouting in rat aortic ring assay. Moreover, P. longum was able to inhibit the VEGF-induced proliferation, cell migration and capillary-like tube formation of primary cultured human endothelial cells. Hence, the observed antiangiogenic activity of the plant P. longum is related to the regulation of these cytokines and growth factors in angiogenesis-induced animals.
International Immunopharmacology 06/2006; 6(5):733-41. · 2.38 Impact Factor
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ABSTRACT: In this study, we explored the antioxidant and anti-inflammatory properties of the medicinal herb Andrographis paniculata using in vitro as well as in vivo systems. Methanolic extract of Andrographis paniculata was found to inhibit formation of oxygen derived free radicals such as superoxide (32%) hydroxyl radicals (80%) lipid peroxidation (80%) and nitric oxide (42.8%) in in vitro system. In vivo studies using BALB/c mice models also showed significant inhibition in PMA induced superoxide (32.4%) and nitric oxide (65.3%) formation. Interestingly we also found that, administration of Andrographis paniculata extract produced complete inhibition of carageenan induced inflammation compared with control models.
Immunopharmacology and Immunotoxicology 02/2006; 28(1):129-40. · 1.83 Impact Factor
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ABSTRACT: Effect of sulforaphane on cell-mediated immune (CMI) response was studied in normal as well as Ehrlich ascites tumor-bearing BALB/c mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) also was enhanced significantly in both normal as well as tumor-bearing animals after sulforaphane administration compared with untreated control tumor-bearing animals. An early antibody-dependent complement-mediated cytotoxicity (ACC) also was observed in sulforaphane-treated normal and tumor-bearing animals. Administration of sulforaphane significantly enhanced the production of Interleukin-2 and Interferon-gamma in normal as well as tumor-bearing animals. In addition, sulforaphane significantly enhanced the proliferation of splenocytes, bone marrow cells, and thymocytes by stimulating the mitogenic potential of various mitogens such as concanavalin A, phytohaemagglutinin, poke weed mitogen, and lipopolysaccharide.
Immunopharmacology and Immunotoxicology 02/2006; 28(3):443-57. · 1.83 Impact Factor
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ABSTRACT: The effect of Thuja occidentalis extract on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. The extract was administered by three different modalities. A remarkable reduction in tumor-nodule formation was shown by simultaneous (74.4%) and prophylactic (71.5%) mode of administration. The effect was comparatively low in drug administration after tumor development (60.2%). Increased lung collagen hydroxyproline (21.13 microg/mg protein) in the metastasized lungs of control animals compared with normal animals (0.98 microg/mg protein) was significantly reduced in Thuja-treated animals. The elevated level of uronic acid (349.5 microg/100 mg tissue) and hexosamine contents in metastatic control animals was significantly reduced in the animals treated with alcoholic extract of Thuja. Similarly the elevated levels of serum sialic acid and serum gamma glutamyl transpeptidase activity in the untreated control animals was significantly reduced in the animals treated with the extract of Thuja. The lifespan of the Thuja treated animals also was seen to be significantly increased.
Immunopharmacology and Immunotoxicology 02/2006; 28(2):269-80. · 1.83 Impact Factor
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ABSTRACT: The effect of Thuja occidentalis against damage induced by gamma radiation was studied. Whole-body exposure of Swiss albino mice to gamma-rays (6 Gy) reduced the total white blood cell count to 1900 cells/mm(3) on the third day, which was elevated to 2050 cells/mm(3) by the administration of alcoholic extract ofT occidentalis (5 mg/dose/animal, intraperitoneally). Six animals from each group were killed after 2, 7, and 11 days of irradiation to detect the bone marrow cellularity and radiation-induced toxicity. The number of bone marrow cells and alpha-esterase positive cells in control animals after 11 days was reduced to 12.2 x 10(6) cells/femur and 693.5/4000 cells, respectively. In T occidentalis-treated animals, bone marrow cellularity was increased to 16.9 x 10(6) cells/femur and alpha-esterase positive cells were 940/4000 cells, a nearly normal level. Alcoholic extract of T occidentalis reduced the elevated levels of GPT and alkaline phosphatase in liver and serum after irradiation. The lipid peroxidation levels were also lowered in the irradiated animals treated with the Thuja extract.
Integrative Cancer Therapies 01/2006; 4(4):322-8. · 2.14 Impact Factor
