Nand K. Sah

Biology of Cox-2: An Application in Cancer Therapeutics

Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in the conversion of arachidonic acid to prostaglandin and other eicosanoids. Molecular pathology studies have revealed that Cox-2 is over-expressed in cancer and stroma cells during tumor progression, and anti-cancer chemo-radiotherapies induce expression of Cox-2 in cancer cells. Elevated tumor Cox-2 is associated with increased angiogenesis, tumor invasion and promotion of tumor cell resistance to apoptosis. Several experimental and clinical studies have established potent anti-cancer activity of NSAID (Non-steroidal anti-inflammatory drugs) and other Cox-2 inhibitors such as celecoxib. Much attention is being focused on Cox-2 inhibitors as beneficial target for cancer chemotherapy. The mode of action of Cox-2 and its inhibitors remains unclear. Further clinical application needs to be investigated for comprehending Cox-2 biological functions and establishing it as an effective target in cancer therapy.

Host-pathogen interactions during apoptosis.

Host pathogen interaction results in a variety of responses, which include phagocytosis of the pathogen, release of cytokines, secretion of toxins, as well as production of reactive oxygen species (ROS). Recent studies have shown that many pathogens exert control on the processes that regulate apoptosis in the host. The induction of apoptosis upon infection results from a complex interaction of parasite proteins with cellular host proteins. Abrogation of host cell apoptosis is often beneficial for the pathogen and results in a successful host invasion. However, in some cases, it has been shown that induction of apoptosis in the infected cells significantly imparts protection to the host from the pathogen. There is a strong correlation between apoptosis and the host protein translation machinery: the pathogen makes all possible efforts to modify this process so as to inhibit cell suicide and ensure that it can survive and, in some cases, establish latent infection. This review discusses the significance of various pathways/steps during virus-mediated modulation of host cell apoptosis.

Detection of survivin and p53 in human oral cancer: Correlation with clinicopathologic findings

Survivin, an inhibitor of apoptosis, is overexpressed in cancer. It has been implicated in both prevention of apoptosis and cell cycle regulation. We investigated the distribution of antiapoptotic protein survivin in 29 oral squamous cell carcinoma (OSCC) and 16 oral premalignant lesions. It has been suggested that wild‐type p53 represses survivin expression. Therefore, we investigated the status of p53 in relation to survivin to determine the potential involvement in oral tumorigenesis.

Antioxidants prevent UV-induced apoptosis by inhibiting mitochondrial cytochrome c release and caspase activation in Spodoptera frugiperda (Sf9) cells.

Oxidative stress has been shown to be associated with apoptosis (programmed cell death) in a number of cell systems. We earlier reported in vitro cultured Spodoptera frugiperda (Sf9) cells as a model system to study oxidative stress induced apoptosis (J Biosciences 24 (1999) 13) and the inhibition of UV‐induced apoptosis by the baculovirus antiapoptotic p35 protein that acts as a sink to sequester reactive oxygen species (Proc Natl Acad Sci USA 96 (1999) 4838). We now show that UV‐induced apoptosis in Sf9 cells, is preceded by the release of mitochondrial cytochrome c into the cytosol and consequent activation of Sf‐caspase‐1. The inhibitory effect of different antioxidants including scavengers of oxygen radicals such as butylated hydroxyanisole (BHA), alpha tocopherol acetate, benzoate and reduced‐glutathione (GSH) on ultra violet B (UVB)‐induced apoptosis in cultured Sf9 cells was assessed. Both, cytochrome c release as well as Sf‐caspase‐1 activation was inhibited by pre‐treatment with antioxidants such as BHA and alpha tocopherol acetate, suggesting that these antioxidants inhibit apoptosis by acting quite upstream in the apoptosis cascade at the mitochondrial level, as well as downstream at the caspase level.

Indian herb 'Sanjeevani' (Selaginella bryopteris) can promote growth and protect against heat shock and apoptotic activities of ultra violet and oxidative stress

Selaginella bryopteris is a lithophyte with remarkable ressurection capabilities. It is full of medicinal properties, hence also known as ‘Sanjeevani’ (one that infuses life). For lack of credible scientific evidence the plant is not in active use as a medicinal herb. We provide scientific evidence for whyS. bryopteris is known as ‘Sanjeevani’.The aqueous extract ofS. bryopteris possesses growth-promoting activity as well as protective action against stress-induced cell death in a number of experimental cell systems including mammalian cells. Treatment of the cells in culture with 10% aqueous extract enhanced cell growth by about 41% in Sf9 cells and 78% in mammalian cells. Pre-treatment of cells with the Selaginella extract (SE) (1-2x5%) protected against oxidative stress (H2O2)-induced cell death. The killing potential of ultra violet (UV) was also significantly reduced when the cells were pre-treated with SE for 1 h. Thermal radiation suppressed cell growth by about 50%. Pre-treatment of cells with SE for 1 h afforded complete protection against heat-induced growth suppression. SE may possess anti-stress and antioxidant activities that could be responsible for the observed effects. Chemical analysis shows that SE contains hexoses and proteins. Taken together,S. bryopteris extract may help in stress-induced complications including those due to heat shock.

Baculoviral p35 inhibits oxidant-induced activation of mitochondrial apoptotic pathway.

In this study we report that the baculovirus p35 anti-apoptotic protein prevents cell death by quenching free radicals at a very upstream step in the apoptotic pathway. Mitochondria of activated rat peritoneal macrophages as well as Spodoptera frugiperda (Sf9) insect cells, following treatment with oxidants, H(2)O(2)/UVB irradiation, release cytochrome c followed by activation of caspase-3. Transfection of macrophages/Sf9 cells with a construct carrying the p35 gene under the CMV/HSP promoters resulted in p35 expression and consequent arrest of oxidative stress-induced apoptosis. p35 expression also inhibited cytochrome c release from the mitochondria of oxidant-exposed cells and blocked caspase-3 activation.

Invitro culturedSpodoptera frugiperda insect cells: Model for oxidative stress-induced apoptosis

Cellular imbalance in the levels of antioxidants and reactive oxygen species (ROS) is directly associated with a number of pathological states and results in programmed cell death or apoptosis. We demonstrate the use ofin vitro culturedSpodoptera frugiperda (sf9) insect cells as a model to study oxidative stress induced programmed cell death. Apoptosis ofin vitro cultured sf9 cells was induced by the exogenous treatment of H2O2 to cells growing in culture. The AD50 (concentration of H2O2 inducing about 50% apoptotic response) varied with the duration of treatment, batch to batch variation of H2O2 and the physiological state of cells. At 24 h post-treatment with H2O2 AD50 was about 475 Μm. Apoptosis could also be induced byin situ generation of H2O2 by the inhibition of catalase activity upon hydroxylamine treatment. Hydroxylamine acted synergistically with H2O2 with an AD50 of 2.2 mM. DMSO, a free radical scavenger, inhibited H2O2-induced apoptosis thereby confirming the involvement of reactive oxygen species. Exposure of cells to UV radiation (312 nm) resulted in a dose-dependent induction of apoptosis. These results provide evidence on the novel use of insect cells as a model for oxidative stress-induced apoptosis.

Mitochondria can power cells to life and death

ConclusionMitochondria serve as power houses of cells but they also possess ‘covered’ knives to kill the cells. A number of intrinsic and extrinsic factors exist which regulate cell killing by mitochondria. Caspases are comparable to a surgeon’s knife, which can be used to sculpt organisms, get rid of wayward, redundant and incorrigibly damaged cells, but can spell doom if not controlled properly.

Aquacultural, Nutritional and Therapeutic Biology of Delicious Seeds of Euryale ferox Salisb. : A Minireview

BACKGROUND Euryale ferox Salisb. (Makhana) is a rooted macro-hydrophyte, grown as a crop in north Bihar wetlands, India. Makhana refers to yummy pops prepared through mechanical smacking of the baked seeds of E. ferox. New techniques have been evolved to produce pops from seeds at a brisk pace. OBJECTIVE It is specially associated with marital rituals possibly in view of its spermatogenic properties. It has a high amino acid index but a low glycemic value. The plant carries medicinal values against cardiovascular and diabetes-related diseases. Makhana pops with a high volume to mass ratio, is developed as a reliable system for drug delivery in the recent times. RESULTS There is a fair prospect of raising multi-faceted industry based on Makhana culture, harvest, post-harvest safety, preparation of pops and various types of food products therefrom and marketing in areas where water-logging is considered as a curse. It may generate employment and strengthen regional economy propping check on population migration primarily due to non-employment and poverty. CONCLUSION Active research is required to harness this macro-hydrophyte along with co-culture of compatible fish varieties and other hydrophytes into a sustainable livelihood and economic prosperity.