Επίδραση της σουλπιρίδης στο µεταβολισµό προ-καρκινογόνων µέσω κυτοχρωµάτων σε ανθρώπινα καρκινικά κύτταρα πνεύµονα (Master thesis)

Δήμου, Νικόλαος Λ.


There is accumulating evidence that male psychotic patients following treatment with antipsychotics are at low risk in developing cancer, although they are usually heavy smokers. All antipsychotic drugs display a common feature: they are D2-dopaminergic antagonists. The present study investigated the effect of Sulpiride (SULP), a selective D2- antagonist on the pulmonary carcinogen- metabolising profile (CYP1A1, CYP1A2, CYP1B1) of male Wistar rats, and on the human non-small cell lung cancer (NSCLC) cells, A549 and H1299. The effect of SULP on the cell population and the level of D2-receptor expression in the above mentioned cell lines wasalso investigated.The data indicated that SULP markedly repressed the basal and Benzo[a]pyrene (B[α]P)-induced CYP1A1, CYP1A2 and CYP1B1 expression in the rat lung. In H1299 lung cancer cells, SULP also reduced the induction of cytochromes CYP1A1, CYP1A2 and CYP1B1 byB[α]P through down-regulation of critical factors in the AhR regulatory pathway. In contrast, SULP further increased the induction by B[a]P of CYP1A1, CYP1A2 and CYP1B1 in A549 lung cancer cells. As in H1299 so in A549 cells, the AhR regulatory pathway plays an important role in the induction by B[a]P of these cytochromes. The high expression level of D2-Rsdetected in the human lungcancer cells A549 and H1299, indicate a potential direct action of SULP on these receptors. It is of interest also to note that SULP markedly decreased the A549 and H1299 cell population. Taken together these findings indicate that D2-R-linked pathways profoundly play significant roles in pulmonary carcinogenesis and strengthen further our previous findings indicating that D2-Rs regulate the CYP-dependent carginogen metabolism in the liver, a critical parameter in carcinogenesis and detoxification of the body.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Subject classification: Πνεύμονας -- Καρκίνος
Keywords: Σουλπιρίδη,Κυτοχρώματα Ρ-450,Καρκίνος πνεύμονα,Προ-καρκινογόνες ουσίες,Sulpiride,Cytochrome P-450,Pulmonary cancer,Pre-carcinogen substances
URI: http://olympias.lib.uoi.gr/jspui/handle/123456789/29263
Appears in Collections:Διατριβές Μεταπτυχιακής Έρευνας (Masters)

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