Shamee Bhattacharjee

Chemopreventive potential of diallylsulfide, lycopene and theaflavin during chemically induced colon carcinogenesis in rat colon through modulation of cyclooxygenase-2 and inducible nitric oxide synthase pathways

Chemoprevention of colorectal cancer has become essential in the modern industrialized world as cancer of the large bowel has become one of the major causes of cancer mortality, second only to lung cancer. Colon cancer integrates lifestyle factors and multistep genetic alterations, and without preventive intervention, a substantial part of the population is likely to develop colorectal cancer at some point during their lives. Diet and nutrition clearly play a role in the etiology of colon cancer. Inhibitory activity of aqueous suspensions of garlic, tomato and black tea was tested on azoxymethane-induced colon carcinogenesis in Sprague–Dawley rats during earlier studies. In the present study, the protective activity of diallylsulfide and lycopene and theaflavin, important antioxidative ingredients of garlic, tomato and black tea, respectively, was assessed during colon carcinogenesis. The effect was observed on aberrant crypt foci, the preneoplastic lesion. As inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activities is correlated with the prevention of colon cancer, the study continues with the determination of the change in the expression of these proteins. Following treatment, significant reduction in the incidences of aberrant crypt foci (by 43.65% in diallylsulfide, 57.39% in lycopene and 66.08% in theaflavin group) was observed, which was in accordance with the reduced expression of cyclooxygenase-2 and inducible nitric oxide synthase. The effect of the intact source was found to be more pronounced than their components used separately.

Antitumorigenic Potential of Linalool Is Accompanied by Modulation of Oxidative Stress: An In Vivo Study in Sarcoma-180 Solid Tumor Model

Coriander, used as a common food seasoning, contains linalool as the main constituent of its essential oil. In this study, we tested the effect of linalool vis-à-vis that of a conventional chemotherapeutic drug, cyclophosphamide, against solid S-180 tumor-bearing Swiss albino mice. Tumor volume, cell count, cell cycle phase distribution, apoptosis, and proliferation markers indicate that linalool has potent antitumor activity. In vitro and in vivo data suggest that induction of oxidative stress might be responsible for the anticancer effect of linalool. However, interestingly, unlike cyclophosphamide, linalool did not induce myelosuppression or hepatotoxicity in mice as evident from bone marrow cell count, status of hepatic oxidative stress/antioxidant enzymes, and histopathology. Thus, linalool exerted prooxidant effect in tumor tissue and an antioxidant effect in liver. This is also supported by the expression of Nrf-2 and p21, which are considered to be important players in response to oxidative stress. Moreover, administration of linalool modulated the proliferation of spleen cells in tumor-bearing mice challenged with lipopolysaccharide. Finally, the detection of linalool in sera and tumor tissues by HPLC confirmed its bioavailability. In conclusion, linalool showed differential cytotoxicity towards tumor and normal cells in contrast to cyclophosphamide, which is uniformly toxic to both.

Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid

Cinnamic acid (C9H8O2), is a major constituent of the oriental Ayurvedic plant Cinnamomum cassia (Family: Lauraceae). This phenolic acid has been reported to possess various pharmacological properties of which its antioxidant activity is a prime one. Therefore it is rational to hypothesize that it may ameliorate myelosuppression and oxidative stress induced by cyclophosphamide, a widely used chemotherapeutic agent. Commercial cyclophosphamide, Endoxan, was administered intraperitoneally to Swiss albino mice (50mg/kg) pretreated with 15, 30 and 60mg/kg doses of cinnamic acid orally at alternate days for 15days. Cinnamic acid pre-treatment was found to reduce cyclophosphamide induced hypocellularity in the bone marrow and spleen. This recovery was also reflected in the peripheral blood count. Amelioration of hypocellularity could be correlated with the modulation of cell cycle phase distribution. Cinnamic acid pre-treatment reduced bone marrow and hepatic oxidative stress as evident by lipid peroxidation and activity assays of antioxidant enzymes such as superoxide dismutase, catalase and glutathione-S-transferase. The present study indicates that cinnamic acid pretreatment has protective influence on the myelosuppression and oxidative stress induced by cyclophosphamide. This investigation is an attempt and is the first of its kind to establish cinnamic acid as an agent whose consumption provides protection to normal cells from the toxic effects of a widely used anti-cancer drug.

Induction of Apoptosis by Eugenol and Capsaicin in Human Gastric Cancer AGS Cells - Elucidating the Role of p53

BACKGROUND Loss of function of the p53 gene is implicated in defective apoptotic responses of tumors to chemotherapy. Although the pro-apoptotic roles of eugenol and capsaicin have been amply reported, their dependence on p53 for apoptosis induction in gastric cancer cells is not well elucidated. The aim of the study was to elucidate the role of p53 in the induction of apoptosis by eugenol and capsaicin in a human gastric cancer cell line, AGS. MATERIALS AND METHODS AGS cells were incubated with or without various concentrations of capsaicin and eugenol for 12 hrs, in the presence and absence of p53 siRNA. Cell cycling, annexin V and expression of apoptosis related proteins Bax, Bcl-2 ratio, p21, cyt c-caspase-9 association, caspase-3 and caspase-8 were studied. RESULTS In the presence of p53, capsaicin was a more potent pro-apoptotic agent than eugenol. However, silencing of p53 significantly abrogated apoptosis induced by capsaicin but not that by eugenol. Western blot analysis of pro-apoptotic markers revealed that as opposed to capsaicin, eugenol could induce caspase-8 and caspase-3 even in the absence of p53. CONCLUSIONS Unlike capsaicin, eugenol could induce apoptosis both in presence and absence of functional p53. Agents which can induce apoptosis irrespective of the cellular p53 status have immense scope for development as potential anticancer agents.

One new azido bridged dinuclear copper(II) thiosemicarbazide complex: synthesis, DNA/protein binding, molecular docking study and cytotoxicity activity

One new azido bridged dinuclear copper(II) thiosemicarbazide complex, [Cu(L)2(N3)2] (1), has been synthesised from the Schiff base ligand derived from 2-acetyl pyridine and thiosemicarbazide. Complex 1 is characterised by elemental analysis, IR, UV-Vis, ESR spectroscopy, cyclic voltammetry and single crystal X-ray structure analysis. Crystallographic results show that the ligand (HL) is coordinated to the metal in a uninegative tridentate fashion. The DNA binding properties of copper(II) complex 1 are explored by employing UV-vis, fluorescence spectral methods, cyclic voltammetry and also viscosity measurements. In addition, the protein binding behaviour in vitro is studied by multispectroscopic techniques using both BSA and HSA. The cytotoxicity profile of the compound along with a cell line study has also been evaluated. Furthermore, the molecular docking technique has also been used to ascertain the mechanism of action of the complex towards DNA, BSA and HSA. Notably, the in vitro cytotoxicity of complex 1 towards two cell lines (AGS and A549 cancer cells) demonstrates that complex 1 has very good broad spectrum anticancer activity.

Exposure to environmentally relevant concentrations of malathion induces significant cellular, biochemical and histological alterations in Labeo rohita

The extensive use of malathion, an organophosphate pesticide, raises the possibility of its undesirable toxicity to non-target organisms. Agricultural run-off and vector control sprays are the major sources of exposure to this pesticide for aquatic organisms. Some earlier studies have reported the presence of malathion at concentrations ranging from 18.12μg/L to 105.2μg/L in various water samples. In this study, we have tested the hypothesis that these sub-lethal yet environmentally significant concentrations of malathion has serious toxicological implications on the fingerlings of Labeo rohita. Exposure to increasing concentration of malathion (10, 50 and 100μg/L) was reflected in the serum concentration of the pesticide and also in the inhibition of acetylcholinesterase activity in fish brains. Increased abnormalities in liver function test coupled with a rise in the oxidative stress response were observed in gills, liver and kidney. However, the increase in antioxidant enzyme activities like superoxide dismutase and glutathione-S-transferase by malathion exposure suggested a hormetic response. Tissue injury due to malathion was evident from the morphological and nuclear anomalies in the H-E stained sections of gill, liver and kidney. Cell cycle analysis of these organs further fortified the histopathological findings. This study elucidates the sub-lethal toxicity of environmentally relevant malathion concentrations on Labeo rohita which indicates the potential health hazard posed to human beings consuming this fish. This calls for careful application of malathion in areas adjoining to inland fisheries.

Antitumor potential of anethole singly and in combination with cyclophosphamide in murine Sarcoma-180 transplantable tumor model

The clinical outcome of chemotherapy in cancer treatment is limited due to severe side effects. There has been a mixed response in experimenting with combinations of conventional chemotherapy with dietary agents to improve the therapeutic outcome. This study is aimed to explore the anti-tumor potential of a spice-derived phytochemical, anethole singly and in combination with cyclophosphamide. Various doses of anethole (10, 20 and 40 mg kg−1) were administered orally on alternate days to Sarcoma-180 solid tumor bearing Swiss albino mice on appearance of palpable tumor. Cyclophosphamide (100 mg kg−1) was injected into anethole treated or untreated tumor bearing mice for 3 consecutive days before sacrifice. Results demonstrated that anethole and cyclophosphamide, singly as well as in combination, reduced tumor load to a significant extent. Cell cycle analysis revealed that cyclophosphamide and cyclophosphamide+anethole exhibited significantly more tumoricidal activity than anethole alone. AnnexinV/PI assay suggested that necrosis was the principal means of tumor reduction when cyclophosphamide was used alone or in combination contrasting to the induction of apoptosis in anethole-treated groups. The necrotic cell death was also reflected in tumor histology. Although no additive effect in tumor reduction was observed with combinatorial treatment, use of anethole was instrumental in reducing the side-effects namely myelosuppression, hepatotoxicity and urotoxicity of cyclophosphamide treatment. The hepatoprotective effect of anethole was further proven by its ability to reduce CCl4 induced hepatotoxicity. This study indicates that anethole pre-treatment protected the bone marrow, liver and urinary bladder from the adverse toxicity of cyclophosphamide without interfering with its anticancer effect.

Wastewater Aquaculture by the Mudialy Fisherman's Cooperative Society in Kolkata, West Bengal: An Example of Sustainable Development

At the heart of one of the most densely populated mega-cities of India lies an eco-friendly and sustainable developmental business model. The city in question is Kolkata and the profitable but environmentally friendly venture that will be highlighted in this paper is that of wastewater-fed aquaculture practiced by a cooperative run by the local fishermen, namely Mudialy Fishermans Cooperative Society (MFCS). Initially the marshy wetlands of Mudialy used to be flooded with polluted waste water from the city and the local industrial complex. Ultimately, the polluted water was released to the sacred River Ganges. This cooperative society has radically transformed these wetlands into an urban fishery and a water-front recreational ecosystem. The present paper focuses on the incredible task completed by the MFCS and also reports the results of water-quality analyses to ascertain that conditions in the water bodies of MFCS are ideal for a profitable aquaculture practice. All the water quality parameters studied (physicochemical water parameters, concentration of different heavy metals, and zooplankton community structure) were well within the normal limits from the point of view of pisciculture. This proves the efficiency of the wastewater purification system adopted by the cooperative society. The major advantage of wastewater-fed aquaculture over conventional wastewater treatment is the large diversity of marketable products and therefore broad possibilities of income generation. Thanks to the poor fishermen of MFCS, the water drained from these wetlands into the River Ganges is no longer polluted.

Cytotoxicity activity, in silico molecular docking, protein- and DNA-binding study of a new Ni(II) Schiff base complex

Abstract One new nickel(II) complex, [Ni(L)] (1), was synthesized from the Schiff base ligand derived from pyrrole-2-carboxaldehyde and 1,3-diaminopropane. Complex 1 was characterized by elemental analysis, IR, UV-Vis and ESI mass spectroscopy, cyclic voltammetry, and single-crystal X-ray structure analysis. Crystallographic results show that two Ni(II) monomeric moieties are present with similar structural features but with slightly different bond lengths and bond angles. The geometry around the Ni(II) center is distorted square planar. DNA-binding properties of complex 1 were well explored by employing UV-Vis and fluorescence spectral methods, cyclic voltammetry, and by viscosity measurements. Similarly the protein-binding study was studied by multispectroscopic techniques using both BSA and HSA. The cytotoxicity study of the compound has also been evaluated. Notably, the in vitro cytotoxicity of complex 1 on two cancer cell lines (AGS and A549) demonstrates that complex 1 has very good anticancer activity. MTT assay, cell-cycle analysis, and annexin-V assay have been performed to know the extent of effect of complex 1 as anticancer agent. Further, in silico molecular docking study revealed that the nickel(II) complex fits into the minor groove of duplex DNA by hydrophobic interaction with functional groups of B-DNA. Graphical Abstract

Example of two novel thiocyanato bridged copper (II) complexes derived from substituted thiosemicarbazone ligand: Structural elucidation, DNA/albumin binding, biological profile analysis and molecular docking study

Abstract Two novel copper (II) substituted thiosemicarbazone Schiff base complexes [Cu(L1)(µ-SCN)]n(NO3)2 (1) and [Cu2(µ-SCN)(SCN)(L2)2](NO3) (2) have been synthesized by condensing substituted thiosemicarbazides like 4-methyl-3-thiosemicarbazide or 4-ethyl-3-thiosemicarbazide with 2-acetylpyridine. Both the metal complexes 1 and 2 are characterized using different spectroscopic techniques like IR, UV-Vis, ESR spectroscopy followed by elemental analysis, cyclic voltammetric measurement and single crystal X-ray structure analysis. X-ray crystal structure analysis reveal that complex 1 is polymeric while complex 2 is dimeric in nature. The coordination geometry around Cu(II) are square pyramidal in which thiosemicarbazone Schiff base ligand coordinate to the central Cu(II) atom in tridentate fashion. The prominent interaction patterns of 1 and 2 with CT-DNA were examined by employing electronic absorption and emission spectral titrations, cyclic voltammetry and viscosity measurements. All the results show that CT-DNA binds with both copper (II) complexes 1 and 2. Furthermore, protein binding ability in vitro of complexes 1 and 2 with both BSA and HSA were carried out using multispectroscopic techniques and a static quenching pattern was observed in both cases. Molecular docking study was employed to ascertain the exact mechanism of action of 1 and 2 with DNA and protein molecules (BSA and HSA). In vitro cytotoxicity activity of complexes 1 and 2 toward AGS and A549 was evaluated using MTT assay which demonstrates that both complexes 1 and 2 have superior prospectus to act as anticancer agents. Communicated by Ramaswamy H. Sarma