Girija Kuttan

Midwestern University, Glendale, AZ, United States

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Publications (194)345 Total impact

  • Vishnu Priya Murali, Girija Kuttan
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    ABSTRACT: Cyclophosphamide (CTX) is a synthetic antineoplastic drug with severe and life-threatening side effects. Studies in search of protective agents, preferably natural products, that can alleviate these side effects are valuable because they can contribute to improve current chemotherapeutic treatment strategies. Curculigo orchioides Gaertn (family Hypoxidaceae) is well known for its medicinal use in the Indian Ayurvedic system of medicine, and various studies have been reported that proved its immunomodulatory and anti-inflammatory properties. In this study, the tumor reduction capacity of CTX in combination with C orchioides methanolic extract was studied using Dalton's lymphoma ascites-induced solid tumor models. Effect of C orchioides on the reversal of the damage induced by CTX administration (intraperitoneally) was also determined in this study. For this, solid tumor volume, serum cytokine levels, hematolological parameters, intestinal histopathology, and serum and tissue biochemical parameters (Glutathione [GSH], alkaline phosphatase [ALP], glutamate pyruvate transaminase [GPT], lipid peroxidation [LPO]) were analyzed. Immune suppression and increased serum proinflammatory cytokine levels caused by CTX administration (25 mg/kg body weight) were reversed by C orchioides (20 mg/kg body weight). The alcoholic extract enhanced the tumor reduction capacity of CTX and reduced GPT and ALP levels in liver and serum, which were elevated by CTX administration. The LPO level was also lower in the CTX-administered animals when treated with the C orchioides extract. In conclusion, the plant extract when administered in combination with CTX, can result in enhanced anticancer properties; it also ameliorates the toxic side effects of CTX. © The Author(s) 2015.
    Integrative Cancer Therapies 01/2015; · 2.01 Impact Factor
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    ABSTRACT: In this study, the antimetastatic potential of the ethanolic extract of Aerva lanata was evaluated using the B16F-10 melanoma-induced lung metastasis model. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with A lanata inhibited tumor nodule formation in the lungs (70.53%), and there was a 65.3% increase in the survival rate of metastatic tumor-bearing animals. These results correlated with biochemical parameters such as lung collagen hydroxyproline, hexosamine, and uronic acid contents; serum sialic acid and γ-glutamyl transpeptidase levels; and histopathological analysis. In vitro studies using B16F-10 cells showed that A lanata inhibited migration of tumor cells, cell invasion through type-I collagen-coated polycarbonate filter and activation of matrix metalloproteinases. Treatment with A lanata induced apoptotic response, characterized by apoptotic morphology, a typical ladder of DNA fragmentation, and detection of 3' hydroxyl ends in DNA by TUNEL assay. There was an increase in the percentage of cells in the sub-G0/G1 phase indicating cell cycle arrest. A lanata treatment resulted in downregulation of bcl-2 and cyclin-D1 expression and upregulation of p53, bax, caspase-9, caspase-3, p21, and p27 gene expression in B16F-10 cells. Proinflammatory cytokine production and gene expression were also found to be downregulated in A lanata-treated cells.
    Integrative Cancer Therapies 11/2012; · 2.01 Impact Factor
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    Poyil Pratheeshkumar, Girija Kuttan
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    ABSTRACT: Effect of Vernonia cinerea L. and vernolide-A on cell-mediated immune (CMI) response was studied in normal as well as tumor-bearing BALB/c mice. Administration of V. cinerea and vernolide-A 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) and antibody-dependent complement-mediated cytotoxicity (ACC) were also enhanced significantly in both normal as well as tumor-bearing animals after V. cinerea and vernolide-A administration compared with untreated control tumor-bearing animals. Extract and vernolide-A showed a significant increase in cytotoxic T lymphocyte (CTL) production in both the in vivo and in vitro models. The level of cytokines such as interleukin (IL)-2 and interferon (IFN)-γ were also enhanced by the treatment of V. cinerea and vernolide-A in both normal as well as tumor-bearing animals. This study demonstrated that V. cinerea extract and vernolide-A stimulate the CTL, NK cell, ADCC, and ADCC through enhanced secretion of IL-2 and IFN-γ.
    Immunopharmacology and Immunotoxicology 02/2012; 34(1):46-55. · 1.36 Impact Factor
  • K S Siveen, Girija Kuttan
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    ABSTRACT: Plant-derived natural products such as alkaloids, flavonoids, terpenoids, and polysaccharides have received considerable attention in recent years due to their diverse pharmacological properties such as immunomodulatory, anti-inflammatory, cytotoxic, cancer chemopreventive effects, and so on. 10-Methoxycanthin-6-one, a β-carboline alkaloid from the medicinal plant Aerva lanata, was assessed for immunomodulatory activity in Balb/c mice. Intraperitoneal administration of five doses of the compound at 0.5 mg/kg body weight was found to enhance the total WBC count (13,975.50 ± 324.27 cells/mm³ on the 12th day), bone marrow cellularity (23.08 ± 0.86 × 10⁶ cells/femur), and number of α-esterase-positive cells (1283.16 ± 21.10 cells/4000 cells). Treatment with the compound along with the antigen, sheep red blood cells, produced an enhancement in the circulating antibody titer (1024 on Days 12 and 15) and the number of plaque-forming cells (PFC) in the spleen. In treated group, maximum number of PFC (264.83 PFC/10⁶ spleen cells) was observed on the sixth day after antigen administration. At the same time, administration of 10-methoxycanthin-6-one could significantly reduce the elevated levels of proinflammatory cytokines and nitric oxide production by lipopolysaccharide (LPS)-stimulated macrophages. There was also a significant reduction in the mRNA levels of inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor alpha (TNF)-α, and interleukin (IL)-1β and IL-6 in LPS-stimulated macrophages after treatment with 10-methoxycanthin-6-one.
    Immunopharmacology and Immunotoxicology 02/2012; 34(1):116-25. · 1.36 Impact Factor
  • A Gulati, E S Sunila, G Kuttan
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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. · 0.51 Impact Factor
  • T P Hamsa, Girija Kuttan
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    ABSTRACT: Berberine, a naturally occurring isoquinoline alkaloid, is present in a number of important medicinal plants. Berberine has a wide range of biochemical and pharmacological effects, including anticancer effects. In this study, we elucidated the mechanism of antiangiogenic activity of berberine using in vivo and in vitro models. In vivo antiangiogenic activity was studied using B16F-10 melanoma cells and induced capillary formation in C57BL/6 mice. Berberine, at 10 mg/kg body weight, showed significant inhibition in tumor-directed capillary formation and in various proangiogenic factors, such as vascular endothelial growth factor (VEGF), and proinflammatory mediators, such as interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), and granulocyte macrophage colony-stimulating factor (GM-CSF), which are involved in tumor angiogenesis. At the same time, it could also increase antitumor factors, such as IL-2 and tissue-inhibitor metalloproteinase (TIMP) levels in the serum. Berberine could also inhibit endothelial motility, migration, tube formation, and vessel sprouting from rat aortic ring in vitro. Further, berberine inhibited various transcription factors involved in tumor development and angiogenesis, such as NF-ĸB, c-Fos, CREB, and ATF-2. mRNA expression levels of proangiogenic factors, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and hypoxia-inducible factor (HIF), were also downregulated in tumor cells after treatment with berberine. Drastically elevated expressions of HIF and VEGF mRNA by tumor cells under hypoxic conditions were also decreased after treatment with berberine. This result clearly demonstrates that the antiangiogenic activity of berberine is mainly mediated through the inhibition of various proinflammatory and pro-angiogenic factors and the major ones are HIF, VEGF, COX-2, NO, NF-ĸB, and proinflammatory cytokines.
    Drug and Chemical Toxicology 01/2012; 35(1):57-70. · 1.10 Impact Factor
  • K S Siveen, Girija Kuttan
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    ABSTRACT: Cell-mediated immunity offers protection against virus-infected cells and tumor cells, involves activation of natural killer (NK) cells, production of antigen-specific cytotoxic T-lymphocytes, and release of various cytokines in response to an antigen. Administration of an ethanolic extract of Aerva lanata was found to stimulate cell-mediated immunological responses in normal and tumor-bearing BALB/c mice. A significant enhancement in NK cell activity in both normal and tumor-bearing hosts was observed after administration of A. lanata. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) were significantly enhanced as well in both sets of treated hosts. In addition, in vivo production of IL-2 and IFNg were each significantly enhanced by extract treatment. The stimulatory effect of A. lanata on cytotoxic T-lymphocyte (CTL) production was determined by Winn's neutralization assay using CTL-sensitive EL4 thymoma cells. A. lanata treatment caused a significant increase in CTL production in both in vivo and in vitro models, in each case as indicated by a significant increase in the life-spans of tumor-injected mice. Taken together, all of these results in the murine model indicate that administration of an ethanolic extract of A. lanata could enhance the cell-mediated anti-tumor response.
    Journal of Immunotoxicology 11/2011; 9(1):25-33. · 1.57 Impact Factor
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    ABSTRACT: Cancer is a major public health problem in India and many other parts of the world. Its two main characteristics are uncontrolled cell growth and metastasis. Natural products represent a rich source of compounds that have found many applications in various fields of medicines and therapy including cancer therapy. Effective ingredients in several plant-derived medicinal extracts are terpenoid compounds and many terpenes have biological activities and are used for the treatment of human diseases. This review attempted to collect all available published scientific literature of eight naturally occurring terpenoids and their effect on inhibition of tumor progression. The present review is about eight potent naturally occurring terpenoids that have been studied for their pharmacological properties in our lab and this review includes 130 references compiled from all major databases. Literature survey revealed that triterpenoids, such as glycyrrhizic acid, ursolic acid, oleanolic acid, and nomilin, the diterpene andrographolide, and the monoterpenoids like limonene and perillic acid had shown immunomodulatory and antitumor activities. All of them could induce apoptosis in various cancer cells by activating various proapoptotic signaling cascades. Many of these terpenoids found to inhibit metastatic progression and tumor-induced angiogenesis. The molecular mechanisms that involved in these activities include inhibition of various oncogenic and anti-apoptotic signaling pathways and suppression or nuclear translocation of various transcription factors including nuclear factor kappa B (NF-κB). The chemopreventive and chemoprotective effects of these compounds point toward their possible role in modern anticancer therapies.
    Pharmaceutical Biology 10/2011; 49(10):995-1007. · 1.21 Impact Factor
  • T P Hamsa, Girija Kuttan
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    ABSTRACT: The present study demonstrated the potential antimetastatic and antiinvasive effect of berberine using both in vivo mouse lung metastasis and in vitro models. Administration of berberine resulted in significant suppression of B16F-10 melanoma induced tumor nodule formation and enhanced the survival of tumor-bearing mice. Berberine treatment also decreased various biochemical parameters associated with lung metastasis. These inhibitory actions may be due to the significant suppression of several signaling molecules such as ERK1/2, NF-κB, ATF-2 and CREB involved in the transcription signaling pathways for MMP gene expression. It could also inhibit the migration and invasion of highly metastatic murine melanoma cells in a dose-dependent manner in vitro. The results clearly show that berberine could significantly inhibit experimental lung metastasis produced by intravenous injection of B16F-10 melanoma cells and this effect could be linked to the down-regulation of metastasis-related signaling molecules.
    Phytotherapy Research 09/2011; 26(4):568-78. · 2.40 Impact Factor
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    Kodappully S Siveen, Girija Kuttan
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    ABSTRACT: The antimetastatic potential of thujone, a naturally occurring monoterpene, was evaluated. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Administration of thujone (1 mg·(kg body weight)(-1)), prophylactically and simultaneously with tumor induction, inhibited tumor nodule formation in the lungs by 59.45% and 57.54%, respectively, with an increase in the survival rate (33.67% and 32.16%) of the metastatic tumor bearing animals. These results correlated with biochemical parameters such as lung collagen hydroxyproline, hexosamine and uronic acid contents, serum sialic acid and γ-glutamyl transpeptidase levels, and histopathological analysis. Treatment with thujone downregulated the production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and granulocyte-monocyte colony-stimulating factor. Thujone administration downregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, extracellular signal-regulated kinase (ERK)-1, ERK-2, and vascular endothelial growth factor (VEGF) and also upregulated the expression of nm-23, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 in the lung tissue of metastasis-induced animals. Treatment with thujone inhibited the activity of MMP-2 and MMP-9 in gelatin zymographic analysis. Thujone treatment significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix in a Boyden chamber. Thujone also inhibited the adhesion of tumor cells to collagen-coated microtire plate wells and the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. These results indicate that Thujone can inhibit the lung metastasis of B16F-10 cells through inhibition of tumor cell proliferation, adhesion, and invasion, as well as by regulating expression of MMPs, VEGF, ERK-1, ERK-2, TIMPs, nm23, and levels of proinflammatory cytokines and IL-2 in metastatic animals.
    Canadian Journal of Physiology and Pharmacology 09/2011; 89(10):691-703. · 1.56 Impact Factor
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    P Pratheeshkumar, Girija Kuttan
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    ABSTRACT: One of the major reasons for the rapid progression of cancers is the ability of tumor cells to escape from the immune surveillance mechanism of the body. Modulation of immune responses is highly relevant in tumor cell destruction. Effect of vernolide-A on the cell-mediated immune (CMI) response in metastatic condition was studied using C57BL/6 mice model. Administration of vernolide-A enhanced natural killer (NK) cell activity, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent complement-mediated cytotoxicity (ACC) and the activity was observed in treated group much earlier compared with the metastatic tumor-bearing control. Administration of vernolide-A significantly enhanced the production of interleukin (IL)-2 and interferon-gamma (IFN-γ) in metastatic tumor-bearing animals. In addition, vernolide-A significantly down-regulated the serum levels of proinflammatory cytokines such as IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) during metastasis. All these results demonstrate that vernolide-A could enhance the immune response against metastatic progression of B16F-10 melanoma cells in mice.
    Immunopharmacology and Immunotoxicology 09/2011; 33(3):533-8. · 1.36 Impact Factor
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    K S Siveen, Girija Kuttan
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    ABSTRACT: Thujone, a naturally occurring monoterpene, was found to enhance the total WBC count, bone marrow cellularity, number of α-esterase positive cells, number of plaque forming cells in spleen and circulating antibody titer in Balb/c mice (1mg/kg body weight, intraperitoneally for 5 days). Thujone treatment enhanced proliferation of splenocytes and thymocytes, both in the presence and absence of specific mitogens. Administration of Thujone was found to stimulate the cell-mediated immunological response in normal and tumor bearing Balb/c mice. A significant enhancement in natural killer (NK) cell mediated cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement mediated cytotoxicity (ACC) in both normal as well as tumor-bearing animals was observed after the administration of Thujone. Production of cytokines such as IL-2 and IFN-γ was significantly enhanced by the administration of Thujone. The stimulatory effect of Thujone on cytotoxic T lymphocyte (CTL) generation was determined by Winn's neutralization assay using CTL sensitive EL4 thymoma cells. Thujone treatment showed a significant increase in CTL production in both the in vivo and in vitro models, as indicated by a significant increase in the life span of tumor bearing animals. All these results indicate that administration of Thujone could enhance the immune response of mice. There was a significant reduction in solid tumor development, mediated by the presence of alert immune responses during Thujone administration.
    International immunopharmacology 08/2011; 11(12):1967-75. · 2.21 Impact Factor
  • Poyil Pratheeshkumar, Girija Kuttan
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    ABSTRACT: Angiogenesis is a crucial step in the growth and metastasis of cancers. Antiangiogenic activity of nomilin was studied using in vivo as well as in vitro models. Nomilin significantly inhibited tumor directed capillary formation. Serum proinflammatory cytokines such as IL-1β, IL-6, TNF-α and GM-CSF and also serum NO levels were significantly reduced by the treatment of nomilin. Administration of nomilin significantly reduced the serum level of VEGF, a proangiogenic factor and increased the antiangiogenic factors IL-2 and TIMP-1. In vitro studies using rat aortic ring assay showed that administration of nomilin at non-toxic concentrations significantly inhibited microvessel sprouting. Studies using human umbilical vein endothelial cells clearly demonstrated that administration of nomilin significantly retarded endothelial cell proliferation, migration, invasion and tube formation. These data clearly demonstrate the antiangiogenic potential of nomilin by downregulating the activation of MMPs, production of VEGF, NO and proinflammatory cytokines as well as upregulating IL-2 and TIMP.
    European journal of pharmacology 08/2011; 668(3):450-8. · 2.59 Impact Factor
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    ABSTRACT: Homoeopathic medicines treat diseases, including cancer, using ultradiluted preparations. Earlier studies indicated that homoeopathic medicines are cytotoxic to tumor cells and reduced animal tumors. However, the mechanism of homoeopathic medicines at the cellular level is not known. The following drugs were used in the study: Ruta 200C, Carcinosinum 200C, Hydrastis 200C, Thuja 200C, and Thuja 1M. These drugs were tested for their ability to induce apoptosis as seen by morphology, DNA laddering, expression of genes related to apoptosis, and TUNEL assay. Similarly, the effect of homoeopathic medicines on apoptosis was measured by microarray analysis. Activity of Ruta 200C was compared with that of the mother tincture. Ruta 200C produced morphological changes in the Dalton's lymphoma ascites tumor cells and induced DNA laddering. Carcinosinum 200C increased apoptotic gene p53 and Ruta 200C decreased antiapoptotic gene Bcl2. Administration of potentiated homoeopathic drugs to tumor-bearing mice induced TUNEL-positive cells in the tumor, showing increased apoptosis of tumor cells. Microarray analysis of cells treated with homoeopathic drugs indicated that many enzymes related to apoptosis were increased by homoeopathic drugs. These data indicate that apoptosis is one of the mechanisms of tumor reduction of homeopathic drugs. A comparison of potentiated drugs with their mother tincture indicated that the potentiated drugs have biological activity similar to that of their mother tincture in spite of ultradilution.
    Integrative Cancer Therapies 07/2011; 11(2):172-82. · 2.01 Impact Factor
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    Poyil Pratheeshkumar, Girija Kuttan
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    ABSTRACT: In this study, we investigated the effect of vernolide-A on the induction of apoptosis as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentrations of vernolide-A showed the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner. Cell-cycle analysis and TUNEL assays also confirmed the observation. The proapoptotic genes, p53, Bax, caspase-9, and caspase-3, were upregulated in vernolide-A-treated cells, whereas the antiapoptotic gene, Bcl-2, was downregulated. vernolide-A treatment also showed a downregulation of cyclin D1 expression and upregulated p21 and p27 gene expression in B16F-10 melanoma cells. The study also reveals that vernolide-A treatment could alter the production and expression of proinflammatory cytokines and could inhibit the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor-κB and other transcription factors, such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response-element-binding protein in B16F-10 melanoma cells. These results suggest that vernolide-A induces apoptosis via activation of p53-induced, caspase-3-mediated proapoptotic signaling and suppression of NF-κB-induced, bcl-2-mediated survival signaling.
    Drug and Chemical Toxicology 07/2011; 34(3):261-70. · 1.10 Impact Factor
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    ABSTRACT: Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli, cabbage, cauliflower, etc. SFN has received a great deal of attention because of its ability to inhibit cell proliferation and induce apoptosis in several tumor cell lines. Previously, we have demonstrated that SFN inhibits the metastasis of B16F-10 melanoma cells in both in vivo and in vitro models. Melanomas are among the aggressive tumor types because of their notorious resistance to treatment and their high tendency to metastasize. In this study, we investigated the influence of SFN on the induction of apoptosis in B16F-10 melanoma cells, which was evidenced by morphological changes such as membrane blebbing, presence of apoptotic bodies, DNA condensation, and also by nuclear DNA fragmentation. SFN-induced apoptosis was associated with the activation of caspases 3 and 9, Bax, and p53 and the downregulation of Bcl-2, caspase-8, Bid, and NF-kB. Caspase-3 is a most likely candidate to mediate SFN-induced apoptosis. In addition to the caspase-dependent pathway, our results also showed the involvement of proinflammatory cytokines, namely tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-12p40, and granulocyte-macrophage colony-stimulating factor (GM-CSF), and the nuclear translocation of factors kappa B (NF-κB) p65, NF-κB p50, NF-κB c-Rel, c-FOS, ATF-2, and CREB-1 in SFN-induced apoptosis. These results raise the possibility that SFN may be a promising candidate for molecular-targeting chemotherapy against melanoma.
    Drug and Chemical Toxicology 07/2011; 34(3):332-40. · 1.10 Impact Factor
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    P Pratheeshkumar, Girija Kuttan
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    ABSTRACT: The inhibitory effect of vernolide-A (C(21)H(28)O(7)) on lung metastasis induced by B16F-10 melanoma cells was studied using C57BL/6 mice. Vernolide-A was administered in three different modalities such as simultaneously with tumor, prophylactic to tumor and after tumor development. Maximum inhibition in the metastasis was observed when vernolide-A was administered simultaneously with tumor. There was 89.39% inhibition of lung tumor nodule formation and 88.51% increase in the life span of metastatic tumor-bearing animals. Highly elevated levels of lung hydroxyproline, lung uronic acid, lung hexosamine, serum sialic acid, serum γ-glutamyl transpeptidase (GGT) and serum vascular endothelial growth factor (VEGF) in the metastatic control animals were found to be significantly lowered in the vernolide-A-treated animals. Histopathological analysis of lung tissues also correlated with these results. Vernolide-A administration downregulated the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, extracellular-signal-regulated kinase-1 (ERK-1), ERK-2 and VEGF in the lung tissue of B16F-10 melanoma challenged animals. In the in vitro system, vernolide-A showed a significant inhibition of invasion of B16F-10 melanoma cells across the collagen matrix. Vernolide-A treatment also inhibited the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. Vernolide-A could inhibit MMP-2 and MMP-9 protein expression in gelatin zymographic analysis of B16F-10 cells. (3)H-thymidine proliferation assay showed that vernolide-A could inhibit the proliferation of B16F-10 melanoma cells in vitro. These results indicate that vernolide-A could inhibit the metastatic progression of B16F-10 melanoma cells in mice.
    Human & Experimental Toxicology 06/2011; 31(1):66-80. · 1.41 Impact Factor
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    P Pratheeshkumar, K Sheeja, Girija Kuttan
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    ABSTRACT: Cancer is a disorder characterized by uncontrolled proliferation and reduced apoptosis. Inducing apoptosis is an efficient method of treating cancers. In this study, we investigated the effect of andrographolide on the induction of apoptosis as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentration of andrographolide showed the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner. Cell cycle analysis and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays also confirmed the observation. The proapoptotic genes p53, Bax, caspase-9, and caspase-3 were found upregulated in andrographolide-treated cells, whereas the antiapoptotic gene bcl-2 was downregulated. This study also reveals that andrographolide treatment could alter the production and expression of proinflammatory cytokines and could inhibit the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor-κB (NF-κB), and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein in B16F-10 melanoma cells. These results suggest that andrographolide induces apoptosis via inhibiting NF-κB-induced bcl-2-mediated survival signaling and modulating p53-induced caspase-3-mediated proapoptotic signaling.
    Immunopharmacology and Immunotoxicology 06/2011; 34(1):143-51. · 1.36 Impact Factor
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    ABSTRACT: Nomilin is a triterpenoid present in common edible citrus fruits with putative anticancer properties. In this study, the authors investigated the antimetastatic potential of nomilin and its possible mechanism of action. Metastasis was induced in C57BL/6 mice through the lateral tail vein using highly metastatic B16F-10 melanoma cells. Administration of nomilin inhibited tumor nodule formation in the lungs (68%) and markedly increased the survival rate of the metastatic tumor-bearing animals. These results correlated with the biochemical parameters and histopathological analysis. Nomilin showed an inhibition of tumor cell invasion and activation of matrix metalloproteinases. Treatment with nomilin induced apoptotic response, characterized by an increase in the sub-G1 fraction of cells with chromatin condensation and membrane blebbing, a typical ladder of DNA fragmentation, and detection of apoptotic cells by TUNEL assay. Nomilin treatment also exhibited a downregulated Bcl-2 and cyclin-D1 expression and upregulated p53, Bax, caspase-9, caspase-3, p21, and p27 gene expression in B16F-10 cells. Proinflammatory cytokine production and gene expression were found to be downregulated in nomilin-treated cells. The study also reveals that nomilin could inhibit the activation and nuclear translocation of antiapoptotic transcription factors such as nuclear factor (NF)-κB, CREB, and ATF-2 in B16F-10 cells.
    Integrative Cancer Therapies 06/2011; 11(1):48-60. · 2.01 Impact Factor
  • T P Hamsa, Girija Kuttan
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    ABSTRACT: Ipomoea obscura (L) is a widely used medicinal plant. In this study, we investigated its anti-inflammatory and anti-tumor effect using in vitro and in vivo models. Methanolic extract of I. obsucra (10 mg/kg b.wt) was given interaperitoneally before inducing inflammation (both acute and chronic) and tumor to mice. I. obscura produced significant inhibition of 55.6%, 42%, and 65% in the paw edema of animals induced by carrageenan, dextran, and formalin respectively. The extract was also a potent inhibitor of lipopolysaccharide (LPS)-induced NO, CRP, and proinflammatory cytokine production via gene expression in peritoneal macrophages. TNF-α production by macrophage culture treated with LPS was found to be significantly inhibited by I. obscura. The extract was 100% toxic at a concentration of 500 µg/mL for both Dalton's lymphoma ascites (DLA) and Ehrlich ascites carcinoma (EAC) cells. The extract was also found to inhibit tumor cell proliferation in a dose and time-dependent manner. It could also inhibit solid tumor development in mice induced with DLA cells and increased life span of mice bearing EAC tumor to 83% and 53.8%, respectively. This anti-inflammatory effect of the extract is assumed to result mainly from the inhibition of some key enzymes and mediators involved in the inflammation and/or cell signaling pathways such as iNOS, COX-2, and proinflammatory cytokines. This anti-inflammatory property might be the reason for its anti-tumor effects.
    Inflammation 06/2011; 34(3):171-83. · 1.92 Impact Factor

Publication Stats

4k Citations
345.00 Total Impact Points

Institutions

  • 2012
    • Midwestern University
      • Department of Pharmaceutical Sciences in Glendale
      Glendale, AZ, United States
  • 2007
    • Kerala Agricultural University
      • College of Veterinary and Animal Sciences
      Thiruvananthapuram, Kerala, India
  • 2002–2003
    • University of Alabama at Birmingham
      • Department of Dermatology
      Birmingham, AL, United States