Biomedical subjects

N T Telang

Publications and source records attributed to N T Telang.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals.

Aberrant proliferation and modulated apoptosis leading to impaired cellular homeostasis represent crucial early events in the multi-step carcinogenic process. Regulation of these perturbed biomarkers may predict efficacious prevention of cancer development. Present experiments on non-cancerous human mammary epithelial 184-B5 cells were designed to examine whether i) exposure to suspect environmental human carcinogen Benzo (a) pyrene (BP) alters the status of cell proliferation and apoptosis and ii) BP-induced alterations are modulated in response to select natural phytochemicals that inhibit rodent mammary tumorigenesis. Flow cytometric analysis, cellular immunoreactivity to proliferation specific and apoptosis specific gene products and anchorage-dependent colony formation represented quantitative endpoints. Cruciferous glucosinolate indole-3-carbinol (I3C), tea polyphenol (-) epigallo catechin gallate (EGCC) and soy isoflavone genistein (GEN) represented the chemopreventive test compounds. A single 24 h exposure to 39 lM BP resulted in a 50% decrease (P=0.02) in the ratio of quiescent (Q=G0) to proliferative (P=S + M) population in part due to increase in aberrantly proliferative cells. The BP-initiated cells also exhibited an 87.8% inhibition (P=0. 0001) in confluency-associated apoptosis and a concomitant decrease in cellular immunoreactivity to wild-type p53. Simultaneous treatment of cultures with BP + I3C, BP + EGCG and BP + GEN resulted in a 1.8- to 3.4-fold increase (P<0.01) in Q/P ratio and 1.8- to 6. 9-fold increase (P=0.001) in sub G0 (apoptotic) population. The induction of apoptosis was accompanied by enhanced p53 immunoreactivity (P<0.01). In long-term (21 day) experiments, BP treatment induced a 145.3% increase (P=0.001) in anchorage-dependent colony formation. This aberrant proliferation was inhibited by 44.2% to 65.3% (P=0.01) in the presence of the three phytochemicals. Thus, BP-induced aberrant proliferation is inhibited by the natural phytochemicals in part due to regulation of cell cycle progression and induction of p53 dependent apoptosis.

Anticarcinogenic Agents↗

PubMedDate not supplied

Modulation of gene expression by selected fatty acids in human breast cancer cells.

The effect of linoleic acid (LNA, n-6) and eicosopentanoic acid (EPA, n-3) was investigated on the parental MCF-7 cells and those transfected with v-H-ras. Transfection of v-H-ras oncogene renders the normally estrogen dependent MCF-7 cells estrogen independent. The effects of LNA and EPA in both the cell lines were measured by their ability to enhance the steady state cytoplasmic mRNA levels of 1-8 and 2-5 A, two genes whose transcription is enhanced in various cells in response to interferons (IFNs). The modulatory effect of these fatty acids on the level of an oncogene HER-2/neu was also investigated. Our results indicate that both the fatty acids induce mRNA 1-8 in parental MCF-7 cells but not in the ras transfected cell line, although the gene is induced in both cell lines in response to IFNs. mRNA 2-5A was not induced by LNA or EPA in either of the cell lines. HER-2/neu levels were enhanced by EPA in MCF-7-ras cells. Our data provide evidence to support the concept that selected, nutritionally relevant, fatty acids can regulate gene expression in vitro. These fatty acids can also induce second messenger signals similar to the ones generated by IFNs.

2',5'-Oligoadenylate Synthetase↗

PubMedDate not supplied

Preneoplastic transformation in mouse mammary tissue: identification and validation of intermediate biomarkers for chemoprevention.

Specific and sensitive markers capable of determining the extent of tumorigenesis are important end points not only for evaluating the carcinogenic potency, but also for assessment of chemopreventive efficacy of modulators. Prototypic mammary carcinogens induce a high frequency of mammary adenocarcinomas. The appearance of tumors, however, is a culmination of initiational and promotional events whose modulation may constitute an effective means for chemopreventive interventions. The purpose of this study was i) to identify intermediate biomarkers for mammary cell transformation and ii) to apply these biomarkers and validate the ability of selected fatty acids to modulate chemical carcinogen-induced tumorigenic transformation. An in vitro model derived from mouse mammary explant cultures was utilized to examine the effects of 7,12 dimethylbenz (a) anthracene (DMBA), a prototype chemical carcinogen for rodent mammary gland. The effects of DMBA exposure were quantified at the molecular level by determining induction of oncogene expression, at metabolic level by determining the extent of estradiol metabolism, and at cellular level by determining the emergence of hormone-independent mammary alveolar lesions (MAL) and their tumorigenic potential. DMBA treatment induced binding of ras oncogene product ras p21 to [alpha 32P] GTP, altered estradiol metabolism by increasing the ratio of C16 alpha/C2 hydroxylation in favor of 16 alpha-OHE1 formation, and exhibited high frequency of MAL. Transplantation of cells from these MAL produced rapidly growing tumors. Treatment of DMBA-exposed cultures with polyunsaturated n-6 fatty acids enhanced, and treatment with polyunsaturated n-3 fatty acid suppressed the molecular, metabolic and cellular intermediate biomarkers for tumorigenic transformation. Thus, oncogene expression, estradiol metabolism and formation of MAL may constitute useful molecular, metabolic and cellular intermediate biomarkers. Alteration of these biomarkers by selected fatty acids is suggestive of their utility as end points for the chemopreventive efficacy of dietary agents.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Modulation in the expression of murine mammary tumor virus, ras proto-oncogene, and of alveolar hyperplasia by fatty acids in mouse mammary explant cultures.

Hyperplastic alveolar nodule, present in the young adult non-lactating but mammary tumor virus harbouring mice (RIII), are biologically active precursor lesions which form mammary tumors at certain age. Using mammary explant cultures from these mice as a model for preneoplastic hyperplasia, we have examined the effects of various fatty acids on the changes in the cellular and molecular markers in vitro. We find that exposure of cultures to omega-6 fatty acids results in -13 fold increase on RT activity, -3 fold increase in expression of c-ras Hp21, and 2 fold increase in the frequency of lactogenic hormone-independent mammary alveolar lesions, MAL. In contrast, exposure of the cultures to eicosapentanoic or stearic acid results in no increase in RT activity, 3-fold decrease in expression of C-ras Hp21, and about 2-fold decrease in MAL frequency. These results suggest that tumor modulating effects of dietary fatty acids may be operative during the initiational and promotional events of viral carcinogenesis, well before the emergence of mammary tumors.

Animals↗