ΑΝΔΡΕΑΣ ΚΩΝΣΤΑΝΤΙΝΟΥ
ΚΩΝΣΤΑΝΤΙΝΟΥ ΑΝΔΡΕΑΣ
CONSTANTINOU ANDREAS
...
ΚΑΘΗΓΗΤΗΣ/ΡΙΑ
Τμήμα Βιολογικών Επιστημών
ΘΕΕ 02 - Σχολή Θετικών και Εφαρμοσμένων Επιστημών
Πανεπιστημιούπολη
B168
22892883
22895095
constantinoulab.ucy.ac.cy

Προσωπικό Προφίλ

Σπούδασε Βιολογία στο Πανεπιστήμιο Αθηνών. Πήρε πτυχίο Master από το Πανεπιστήμιο του Toledo Ohio των Ηνωμένων Πολιτειών και διδακτορικό στη Βιοχημεία από το ιατρικό κολέγιο του Ohio. Κατά τη διάρκεια της μεταδιδακτορικής εργασίας του στο Πανεπιστήμιο Northwestern, ανακάλυψε ένα νέο τρόπο γονιδιακής έκφρασης που δημοσιεύτηκε στο περιοδικό Cell (42:429437, 1985. Ήταν ο πρώτος που ανακάλυψε ότι το φυτό-οιστρογόνο genistein είναι ένας ισχυρός επαγωγέας της διαφοροποίησης καρκινογόνων κυττάρων.Υπήρξε μέχρι τον Ιούλιο του 2002 διευθυντής έρευνας σε πρόγραμμα του Πανεπιστήμιου του Ιλλινόις (Σικάγο), που συμπεριλάμβανε 96 καθηγητές και 27 εταιρίες τροφίμων και φαρμάκων. Προτού έρθει στο Πανεπιστήμιο Κύπρου ήταν αναπληρωτής Καθηγητής στα τμήματα ογκολογίας, μοριακής γενετικής, φαρμακολογίας και ιατρικής χημείας. Είναι βοηθός συντάκτης του περιοδικού Nutrition and Cancer και ειδικός συντάκτης για διάφορα άλλα επιστημονικά περιοδικά. Υπηρετεί σε επιστημονικές συμβουλευτικές επιτροπές καθώς και στο Εθνικό Ίδρυμα Υγείας (ΝΗΙ) των Ηνωμένων Πολιτειών.
Τα ερευνητικά του ενδιαφέροντα περιλαμβάνουν την ανακάλυψη ουσιών που μπορούν να προλάβουν ή να θεραπεύσουν το καρκίνο του μαστού. Διευθύνει ένα πρόγραμμα που αξιολογεί τη χρησιμότητα φασολιών σόγιας και των μοναδικών συστατικών τους στην πρόληψη του καρκίνου του μαστού. Συμμετέχει σε κλινικές μελέτες που αξιολογούν ένα συστατικό των ντοματών για την πρόληψη του καρκίνου του προστάτη. Η έρευνα του χρησιμοποιεί τα καλλιεργημένα κύτταρα, τα ζωικά πρότυπα και τα ανθρώπινα θέματα. Η τρέχουσα έρευνα του χρηματοδοτείται από τα εθνικά ιδρύματα υγείας (5 επιχορηγήσεις και 1 σύμβαση), την Αμερικανική Κοινωνία Καρκίνου (1 επιχορήγηση), το Αμερικανικό Ίδρυμα για την έρευνα καρκίνου (1 επιχορήγηση) και τον ιδιωτικό τομέα (2 επιχορηγήσεις). Αφιέρωσε τις ερευνητικές προσπάθειές του στη μάχη κατά του καρκίνου. Mετά την απόκτηση του Διδακτορικού του τίτλου έκανε μια σημαντική ανακάλυψη που συνέδεσε τη ρυθμιστική υπομονάδα της -εξαρτώμενης από το cAMP πρωτεϊνικής κινάσης με το ένζυμο τοποϊσομεράση Ι του DNA. Η επόμενη έρευνά του αποκάλυψε ότι η genistein, ένα συστατικό της σόγιας, είναι ανασταλτικός παράγοντας της τοποϊσομεράσης ΙΙ και επαγωγέας της διαφοροποίησης καρκινικών κυττάρων. Προσδιόρισε τους μοριακούς μηχανισμούς από τους οποίους η genistein προκαλεί προγραμματισμένο κυτταρικό θάνατο (απόπτωση) στα καρκινογόνα κύτταρα του μαστού. Αξιολογεί τώρα πώς τα τμήματα σόγιας θα μπορούσαν να εμποδίσουν την καρκινογένεση με τη δέσμευση στο δέκτη οιστρογόνου ή με την αντί-οξειδωτική δράση τους. Έχει αναπτύξει μεθόδους αναλύσεως και το χαρακτηρισμού νέων θεραπευτικών φαρμάκων καρκίνου αλλά ενδιαφέρεται επίσης έντονα για την πρόληψη του καρκίνου. Η έρευνά του βασίζεται στην υπόθεση ότι «πάνω από το 50% όλων των καρκίνων μπορεί να προληφθούν με κατάλληλη διατροφή και τροποποίηση του τρόπου ζωής», και επομένως είναι δυνατό να προσδιοριστούν τα τμήματα τροφίμων που μόνα τους, ή σε συνδυασμό, μπορούν να παρέχουν προστασία κατά του καρκίνου.
1. Chakraborty I, Constantinou AI, McCorquodale M. Monoclonal antibodies to sperm surface antigens. Animal Reprod. Science, 9: 101-109, 1985.2.
2. Constantinou AI, Squinto, SP, Jungmann, JA. The phosphoform of regulatory subunit RII of cyclic AMP-dependent protein kinase possesses intrinsic topoisomerase activity. Cell, 43: 429-437, 1985.
3. Jungmann RA, Constantinou AI , Squinto SP, Kwast-Welfeld J, Schweppe JJ. Regulation of lactate dehydrogenase gene expression by cyclic AMP-dependent protein kinase subunits. Ann. N.Y. Acad. Sci. 478: 147-161, 1986.
4. Constantinou AI, Voelkel-Meiman K, Sternglanz R, McCorquodale M, McCorquodale J. Involvement of host DNA gyrase in growth of bacteriophage T5. J. Virology 57: 875-882. 1986.
5. Constantinou AI, Henning-Chubb C, Huberman E. Novobiocin and Phorbol 12-Myristate 13-acetate-induced differentiation of human leukemia cells associated with a reduction in topoisomerase II activity. Cancer Res. 49: 1110-1117, 1989.
6. Hunzicker-Dunn M., Meizels ET, Kern LC, Ekstrom RC, Constantinou AI. Separation of the complexes formed between the regulatory and catalytic subunits of cyclic adenosine monophosphate-dependent protein kinase and topoisomerase I activity in preovulatory folicle-enriched immature rat ovaries. Molecul. Endocrinol. 3: 780-789, 1989.
7. Constantinou AI, Kiguchi K, Huberman E. Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein. Cancer Res., 50: 2618-2624, 1990.
8. Kiguchi K, Constantinou AI, Huberman E. Genistein-induced cell differentiation and protein-linked DNA strand breakage in human melanoma cells. Cancer Communications 2: 271-278, 1990.
9. Ganapathi R, Kamath N, Constantinou AI, Grabowski D, Ford J, Anderson A. Effect of the calmodulin inhibitor trifluoperazine on phosphorylation of p-glycoprotein and topoisomerase II: Relationship to modulation of subcellular distribution, DNA damage and cytotoxicity of doxorubicin in multidrug resistant L1210 mouse leukemia cells. Biochemical Pharm. 41: 21-26, 1991.
10. Constantinou AI, Grdina D, Kiguchi K, Huberman E. The effect of topoisomerase inhibitors on the expression of differentiation markers and cell cycle progression in human K-562 leukemia cells. Exp. Cell Res. 203: 100-103, 1992.
11. Ganapathi R, Zwelling L, Constantinou A, Ford J, Grabowski D. Altered phosphorylation, biosynthesis and degradation of the 170 kDa form of topoisomerase II as a determinant of amsacrine resistance in human leukemia cells. Biochem. Biophys. Res Commun. 192 (3): 1274-1280, 1993.
12. Grdina DJ, Constantinou AI, Shigematsou N. Inhibition of topoisomerase II activity in CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065). Radiation Res., 138: 44-52, 1994.
13. Mehta RG, Liu J, Constantinou AI, Hawthorne M, Pezzuto J, Moon R, Moriaty R. Structure-activity relationships of brassinin in preventing the development of carcinogen-induced mammary lesions in organ culture. Anticancer Res.
14:1209-1214, 1994. 14. Constantinou AI, Huberman E. Genistein, an inducer of tumor cell differentiation: possible mechanisms of action. Proc. Soc. Exper. Biol. Med. 208:109-115, 1995.
15. Mehta RG, Moriaty RM, Liu J, Constantinou AI, Thomas C, Hawthorne M, Pezzuto J, Moon R. Brassinin, a phytoalexin from cabbage: synthesis and activity as cancer chemopreventive agent. Carcinogenesis 16: 399-404, 1995.
16. Constantinou A, Stoner GD, Young-Han, Mehta RG, Runyan C, Moon R. The dietary anticancer agent ellagic acid is a potent inhibitor of human DNA topoisomerases. Nutr. Cancer. 1995, 23:121-130
17. Constantinou A, Mehta, RG, Runyan C, Rao RVN, Vaughan A, Moon, R C. Plant flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationships. J. Natural Products, 58: 217-225, 1995.
18. Mehta RG, Mehta RR, Constantinou AI, Moon RC. Distribution of epidermal growth factor receptors in normal and neoplastic mammary tissues. Oncology Reports 2: 281-284, 1995.
19. Gerhauser C, Woonghon, M, Lee SK, Suh N, Yingde L, Kosmeder J, Luyengi L, Fong HH, Kinghorn DA, Moriaty RM, Mehta RG, Constantinou AI, Moon RC, Pezzuto JM. Rotenoids mediated potent cancer chemopreventive activity through transcriptional regulation of ornithine decarboxylase. Nature Med., 1:260-266, 1995.
20. Ganapathi R, Constantinou AI, Kamath N, Dubyak G, Grabowski D, Krivacic K. Resistance to etoposide in human leukemia HL-60 cells: reduction in drug induced DNA cleavage associated with hypophosphorylation of topoisomerase II phosphopeptides. Molecular Pharmacol. 50: 243-248, 1996.
21. Constantinou AI, Vaughan A, Yamasaki H, Kamath N. Commitment to differentiation in mouse erythroleukemia cells is controlled by alterations in topoisomerase II alpha phosphorylation. Cancer Res. 56:4192-4196, 1996.
22. Constantinou AI, Mehta RG, Vaughan A. Inhibition of N-methyl-N-nitrosourea-Induced Mammary Tumors in Rats by the Soybean Isoflavones. Anticancer Res.,16: 3293-3298, 1996.
23. Mehta RG, Moriaty RM, Mehta RR, Penmasta R, Lazzaro G, Constantinou AI, Knutson JC, Guo L. Prevention of preneoplastic mammary lesion development by a novel vitamin D analog 1alpha(hydroxy)vitamin D5. J. Natl. Cancer Inst., 89: 212-218, 1997.
24. Krygier A, Murley JS, Mehta RR, Constantinou AI. Induction of human adenocarcinoma cell differentiation by the phytoestrogen genistein is independent to its antiestrogenic function . Int J. Oncol. 10:753-757, 1997.
25. Constantinou AI, Runyan C, Grdina D, Murley J. Apoptosis and cell cycle delay in G2-M phase introduced by the phytoestrogen genistein. Phytomedicine (suplement I) 3: 124-125, 1997.
26. Hesser P, Larsen PE, Constantinou AI, Schram KH, Weber JM. Isolation of isoflavones from soy-based fermentations of the erythromycin-producing bacterium Saccharopolyspora erythrea. Appl. Microbiol. Biotechnol 47: 398-404, 1997.
27. Khodarev NA, Narayanna A, Constantinou AI, Vaughan ATM. Topologically constrained domains of supercoiled DNA in eukaryotic cells. DNA and Cell Biology 16: 1051-1058, 1997.
28. Murley JS, Constantinou AI, Grdina DJ. WR-1065, an active metabolite of the cytoprotector amifostine, affects phosporylation of topoisomerase II ? leading to changes in enzyme activity and cell cycle progression in CHO AA8 cells. Cell Proliferation, 30: 283-294, 1997.
29. Krygier A, Mehta RR, Constantinou AI. Genistein induces maturation of human breast cancer cells and prevents tumor growth in nude mice. Am. J. Clin. Nutr, 68 (supl):1426S-30S,1998.
30. Constantinou AI, Kamath N, Murley JA. Genistein inactivates bcl-2, delays G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells. Eur. J. Cancer, 34: 1927-1934, 1998.
31. Boddie AW, Constantinou AI, Williams C, Reed A. Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cell line. Br. J. Cancer, 77:1395-1404, 1998.
32. Aoyama M, Grabowski D, Dubyak G, Constantinou AI, Rybicki L, Bukowski R, Ganapathi M, Hickson I, Ganapathi R. Attenuation of drug stimulated DNA cleavage complex formation and cytotoxicity is associated with alterations in phosphorylation of topoisomerase II alpha. Biochemical Journal, 15:336:723-733, 1998.
33. Xiaoyig Xu, Wang Y, Constantinou AI, Stacewicz-Sapuntzakis M, Bowen P, van Breemen R. Solubilization and stabilization of carotenoids using micelles: Delivery of lycopene to cells in culture. Lipids, 34: 1031-1036, 1999.
34. Constantinou AI, Salti G. Application of Topoisomerase Assays in the Evaluation of Natural Products as Antitumor Agents. Journal of Medicinal Food, 2: 149-153, 1999.35. Salti GI, Das Gupta TK, Constantinou AI. A novel use for the comet assay; detection of topisomerase II inhibitors. Anticancer Res., 20: 3189-3193, 2000.
36. Chen Y, Liu X, Pisha E, Constantinou AI, Hua Y, Shen L, van Breemen RB, Elguindi EC, Blond, SY, Zhang F, Bolton JL. A metabolite of equine estrogens, 4-hydroxyequilenin, induces DNA damage and apoptosis in breast cancer cell lines. Chem. Res. Toxicol.,13: 342-50, 2000.
37. Salti GI, Mehta RJ, Das Gupta TK, Boddie AW, Grewal S, Constantinou AI. Genistein-induced DNA breaks in HT-29 colon cancer cells are mediated by topoisomerase II as detected by the comet assay. Eur. J. Cancer, 36: 796-802, 2000.
38. Cho KH, Pezzuto JM, Bolton JL, Steele VE, Kelloff, GJ, Lee SK, Constantinou AI. Selection of Cancer Chemopreventive Agents Based on Inhibition of Topoisomerase II Activity. Eur. J. Cancer 36: 2146-2156, 2000.
39. Pisha E, Lui X, Constantinou AI, Bolton J. Evidence that a metabolite of equine estrogens, 4-Hydroxyequilenin, induces cellular transformation in vitro. Chem. Res. Toxicol. 14:82-90, 2001.
40. Salti G, Kichina J, Das Gupta T, Uddin S, Bradescu L, Pezzuto J, Mehta R, Constantinou AI. Betulinic acid reduces UV-C-induced DNA breakage in congenital melanocytic neval cells: evidence for potential role as a chemopreventive agent. Melanoma Res. 11:99-104, 2001.
41. Liu J, Burdette JE, Xu H, Gu C, Bhat K, Booth N, Constantinou AI, van Breemen RB, Pezzuto JM, Fong HHS, Farnsworth NR, Bolton JL. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agr. Food Chem. 49: 2472-2479, 2001.
42. Constantinou AI, Lantvit D, Hawthorn M, Xu X, van Breemen R, Pezzuto J. Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats. Nutrition and Cancer 41: 75-81, 2001.
43. Burdette J, Liu J, Lantvit D, Lim E, Booth N, Bhat KPL, van Breemen RB, Constantinou AI, Pezzuto JM, Farnsworth NR, Bolton JL. In vivo estrogenic effects of Trifolium pratense (red clover) in ovariectomized Sprague-Dawley rats. J. Nutr. 132: 27-30, 2002.
44. Constantinou AI, Rossi H, Lantvit D, Hawthorn M, Xu X, Nho C-W, Jefferey EH, Christov K, van Breemen R, Pezzuto J. Soy protein isolate prevents chemically induced rat mammary tumors. Pharmaceutical Biology 40: 24-34, 2002.
45. Block KI, Constantinou A, Hilakivi-Clarke L, Hughes C, Tripathy D, Tice JA. Point-counterpoint: soy intake for breast cancer patients. Integr Cancer Ther, 1: 90-100, 2002.
46. Burdette JE, Chen SN, Lu ZZ, Xu H, White BE, Fabricant DS, Liu J, Fong HH, Farnsworth NR., Constantinou AI, Van Breemen RB, Pezzuto JM,Bolton JL. Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: bioassay-directed isolation and characterization of active principles. J Agric Food Chem, 50: 7022-7028, 2002.
47. Constantinou AI, Husband, A. Phenoxodiol (2H-1-benzopyran-7-0,1,3-(4-hydroxyphenyl)), a novel isoflavone derivative, inhibits DNA topoisomerase II by stabilizing the cleavable complex. Anticancer Res, 22: 2581-2585, 2002.
48. Xu, H., Fabricant, D. S., Piersen, C. E., Bolton, J. L., Pezzuto, J. M., Fong, H., Totura, S., Farnsworth, N. R., and Constantinou, A. I. A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for women's health. Phytomedicine, 9: 757-762, 2002.
49. Constantinou, A. I., Mehta, R., and Husband A. Phenoxodiol, a novel isoflavone derivative, inhibits dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. Eur J Cancer, 39: 1012-1018, 2003.50. Gentile MS, Vasu C, Green A, Murillo G, Das Gupta TK, Constantinou AI, Prabhakar BS, Salti GI. Targeting colon cancer cells with genistein-17.1A immunoconjugate. Int J Oncol, 22: 955-959, 2003.
51. Tonetti DA, Rubenstein R, DeLeon M, Zhao H, Pappas SG, Bentrem DJ, Chen B, Constantinou A, Jordan CV. Stable transfection of an estrogen receptor beta cDNA isoform into MDA-MB-231 breast cancer cells. J Steroid Biochem Mol Biol, 87: 47-55, 2003.
52. Guo JY, Li X, Browning JD Jr, Rottinghaus GE, Lubahn DB, Constantinou A, Bennink M, MacDonald RS, Dietary soy isoflavones and estrone protect ovariectomized ERalphaKO and wild-type mice from carcinogen-induced colon cancer. J Nutr, 134: 179-182, 2004.
53. Punj V, Bhattacharyya S, Saint-Dic D, Vasu C, Cunningham EA, Graves J, Yamada T, Constantinou AI, Christov K, White B, Li G, Majumdar D, Chakrabarty AM, Das Gupta TK. Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer. Oncogene, 23: 2367-2378, 2004.
54. Murillo G, Choi, J, Pan O, Constantinou A, Mehta R. Garbanzo bean flour is as effective as soy bean flour in suppressing the formation of aberrant crypt in the colons of CF-1 mice. Anticancer Res. 24:3049-55 2004.
55. Constantinou AI, White BEP, Tonetti D, Yang Y, Liang W, Li W, van Breemen RB. The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary tumors. European J Cancer, 41: 647-654, 2005
56. Tonetti DA, Zhang Y, Zhao H, Lim SB, Constantinou AI. The effect of the phytoestrogens genistein, daidzein, and equol on the growth of tamoxifen-resistant T47D/PKC alpha. Nutr Cancer 58:222-229, 2007
57. Constantinou C, Papas A and Constantinou AI. Vitamin E and Cancer: An insight into the anticancer activities of vitamin E isomers and analogues. Int J Cancer, 123:739-52, 2008.
58. Georgaki S, Skopeliti M, Tsiatas M, Nicolaou KA, Husband Al, Bamias A, Constantinou AI, Tsitsilonis OE. Phenoxodiol, an anticancer isoflavene, induces immunomodulatory effects in vitro and in vivo. J Cell Mol Med. 20: 1-10, 2009.
59. Batsi C, Markopoulou S, Kontargiris E, Charalambous C, Thomas C, Christoforidis S, Kanavaros P, Constantinou AI, Marcu KB, Kolettas E. Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27(Kip1)-dependent G1/S cell cycle arrest in conjunction with NF-kappaB activation. Biochem Pharmacol. 78:33-44, 2009.
60. Constantinou C, Papas KA, Constantinou AI. Caspase-independent pathways of programmed cell death: the unraveling of new targets of cancer therapy? Curr Cancer Drug Targets 9:717-28, 2009.
61. Constantinou C, Hyatt JA, Vraka PS, Papas A, Papas KA, Neophytou C, Hadjivassiliou V, Constantinou AI. Induction of caspase-independent programmed cell death by vitamin E natural homologs and synthetic derivatives. Nutr Cancer: 61:864-74, 2009.
62. Constantinou C, Neophytou CM, Vraka P, Hyatt JA, Papas KA, Constantinou AI. Induction of DNA Damage and Caspase-Independent Programmed Cell Death by Vitamin E. Nutr Cancer. 64:136-152 2012.
63. Nicolaou KA, Liapis V, Evdokiou A, Constantinou C, Magiatis P, Skaltsounis AL, Koumas L, Costeas PA, Constantinou AI. Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells. Biochem Biophys Res Commun. 425:76-82. 2012.
64. Odiatou EM, Skaltsounis AL, Constantinou AI. Identification of the factors responsible for the in vitro pro-oxidant and cytotoxic activities of the olive polyphenols oleuropein and hydroxytyrosol. Cancer Lett. 330:113-21, 2013. 
65. Charalambous C, Pitta C and Constantinou AI. Equol enhances tamoxifen’s antitumor activity by induction of caspace-mediated apoptosis. BMC Cancer. 13:238-247, 2013.
66. Pitta C, Papagiorges P., Constantinou AI. Combination treatment with TSA and 5-aza-dc restores response to tamoxifen in tamoxifen resistant ER-β negative breast cancer cells. Cancer Lett. 337: 167-176, 2013
67. Cretu E, Karonen M, Salminen JP, Mircea C, Trifan A, Charalambous C, Constantinou AI, Miron A. In vitro study of the antioxidant activity of a polyphenol-rich extract from Pinus brutia bark and its fractions. J Med Food16:984-91, 2013
68. Neophytou CM, Constantinou C, Papageorgis P, Constantinou AI. D-alpha-tocopheryl polyethylene glycol succinate (TPGS) induces cell cycle arrest and apoptosis selectively in Survivin-overexpressing breast cancer cells. Biochem Pharmacology, 2014 (in press).
69. Miron A, Olymbiou C, Charalambous C, Neophytou C, Salminen JP, Karonen  M, Constantinou AI. Chemical composition, antioxidant and antiproliferative  activity of a polyphenol-rich fraction from Pinus sylvestris L. Bark. (in press).

Profile Information

1980 - 1984          Predoctoral Fellow, Department of Biochemistry, Medical College of Ohio, Toledo, Ohio

1984 - 1986          Postdoctoral Fellow, Department of Molecular Biology, Northwestern University Medical School, Chicago, Illinois

1986 - 1990          Postdoctoral Appointee, Division of Biological and Medical Research, Argonne National Laboratory, Argonne, Illinois

1990 - 1992          Research Biologist, IIT Research Institute, Chicago, Illinois

1992 - 1994          Assistant Professor, Specialized Cancer Center and Department of Genetics, School of Medicine, University of Illinois at                            Chicago, Chicago, Illinois

1994 - 1997          Assistant Professor, Department of Surgical Oncology and Department of Genetics, University of Illinois at Chicago, Chicago, Illinois

1997 - 2002          Associate Professor, Department of Surgical Oncology, Department of Genetics and Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois

2000 - 2002          Associate Professor, Medicinal Chemistry/Pharmacognosy, College of Pharmacy University of Illinois at Chicago, Chicago, Illinois

2000 - 2002          Director of Research, Functional Foods for Health (FFH) Program

2004 - 2006          Chairman, Department of Biological Sciences, University of Cyprus

2006 - 2008          Dean, Faculty of Pure and Applied Sciences, University of Cyprus

2009 - 2012          Chairman, Department of Biological Sciences, University of Cyprus

2002 - present      Professor of Molecular Biology, University of Cyprus.

1997 – present     Associate Editor for Nutrition and Cancer, an International Journal

2002 – present     Member, Editorial Board, in vivo.

• Role of nutrition in carcinogenesis; cancer chemoprevention.
• Interactions between botanicals and drugs; especially tamoxifen and soy phytoestrogens.
• Molecular targets of antitumor drugs, especially DNA-topoisomerases.
• Phytoestrogens and Selective Estrogen Receptor Modulators (SERMs).
• Cancer epigenetics and targetted therapeutics.

 

1. Chakraborty I, Constantinou AI, McCorquodale M. Monoclonal antibodies to sperm surface antigens. Animal Reprod. Science, 9: 101-109, 1985.2.
2. Constantinou AI, Squinto, SP, Jungmann, JA. The phosphoform of regulatory subunit RII of cyclic AMP-dependent protein kinase possesses intrinsic topoisomerase activity. Cell, 43: 429-437, 1985.
3. Jungmann RA, Constantinou AI , Squinto SP, Kwast-Welfeld J, Schweppe JJ. Regulation of lactate dehydrogenase gene expression by cyclic AMP-dependent protein kinase subunits. Ann. N.Y. Acad. Sci. 478: 147-161, 1986.
4. Constantinou AI, Voelkel-Meiman K, Sternglanz R, McCorquodale M, McCorquodale J. Involvement of host DNA gyrase in growth of bacteriophage T5. J. Virology 57: 875-882. 1986.
5. Constantinou AI, Henning-Chubb C, Huberman E. Novobiocin and Phorbol 12-Myristate 13-acetate-induced differentiation of human leukemia cells associated with a reduction in topoisomerase II activity. Cancer Res. 49: 1110-1117, 1989.
6. Hunzicker-Dunn M., Meizels ET, Kern LC, Ekstrom RC, Constantinou AI. Separation of the complexes formed between the regulatory and catalytic subunits of cyclic adenosine monophosphate-dependent protein kinase and topoisomerase I activity in preovulatory folicle-enriched immature rat ovaries. Molecul. Endocrinol. 3: 780-789, 1989.
7. Constantinou AI, Kiguchi K, Huberman E. Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein. Cancer Res., 50: 2618-2624, 1990.
8. Kiguchi K, Constantinou AI, Huberman E. Genistein-induced cell differentiation and protein-linked DNA strand breakage in human melanoma cells. Cancer Communications 2: 271-278, 1990.
9. Ganapathi R, Kamath N, Constantinou AI, Grabowski D, Ford J, Anderson A. Effect of the calmodulin inhibitor trifluoperazine on phosphorylation of p-glycoprotein and topoisomerase II: Relationship to modulation of subcellular distribution, DNA damage and cytotoxicity of doxorubicin in multidrug resistant L1210 mouse leukemia cells. Biochemical Pharm. 41: 21-26, 1991.
10. Constantinou AI, Grdina D, Kiguchi K, Huberman E. The effect of topoisomerase inhibitors on the expression of differentiation markers and cell cycle progression in human K-562 leukemia cells. Exp. Cell Res. 203: 100-103, 1992.
11. Ganapathi R, Zwelling L, Constantinou A, Ford J, Grabowski D. Altered phosphorylation, biosynthesis and degradation of the 170 kDa form of topoisomerase II as a determinant of amsacrine resistance in human leukemia cells. Biochem. Biophys. Res Commun. 192 (3): 1274-1280, 1993.
12. Grdina DJ, Constantinou AI, Shigematsou N. Inhibition of topoisomerase II activity in CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065). Radiation Res., 138: 44-52, 1994.
13. Mehta RG, Liu J, Constantinou AI, Hawthorne M, Pezzuto J, Moon R, Moriaty R. Structure-activity relationships of brassinin in preventing the development of carcinogen-induced mammary lesions in organ culture. Anticancer Res.
14:1209-1214, 1994. 14. Constantinou AI, Huberman E. Genistein, an inducer of tumor cell differentiation: possible mechanisms of action. Proc. Soc. Exper. Biol. Med. 208:109-115, 1995.
15. Mehta RG, Moriaty RM, Liu J, Constantinou AI, Thomas C, Hawthorne M, Pezzuto J, Moon R. Brassinin, a phytoalexin from cabbage: synthesis and activity as cancer chemopreventive agent. Carcinogenesis 16: 399-404, 1995.
16. Constantinou A, Stoner GD, Young-Han, Mehta RG, Runyan C, Moon R. The dietary anticancer agent ellagic acid is a potent inhibitor of human DNA topoisomerases. Nutr. Cancer. 1995, 23:121-130
17. Constantinou A, Mehta, RG, Runyan C, Rao RVN, Vaughan A, Moon, R C. Plant flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationships. J. Natural Products, 58: 217-225, 1995.
18. Mehta RG, Mehta RR, Constantinou AI, Moon RC. Distribution of epidermal growth factor receptors in normal and neoplastic mammary tissues. Oncology Reports 2: 281-284, 1995.
19. Gerhauser C, Woonghon, M, Lee SK, Suh N, Yingde L, Kosmeder J, Luyengi L, Fong HH, Kinghorn DA, Moriaty RM, Mehta RG, Constantinou AI, Moon RC, Pezzuto JM. Rotenoids mediated potent cancer chemopreventive activity through transcriptional regulation of ornithine decarboxylase. Nature Med., 1:260-266, 1995.
20. Ganapathi R, Constantinou AI, Kamath N, Dubyak G, Grabowski D, Krivacic K. Resistance to etoposide in human leukemia HL-60 cells: reduction in drug induced DNA cleavage associated with hypophosphorylation of topoisomerase II phosphopeptides. Molecular Pharmacol. 50: 243-248, 1996.
21. Constantinou AI, Vaughan A, Yamasaki H, Kamath N. Commitment to differentiation in mouse erythroleukemia cells is controlled by alterations in topoisomerase II alpha phosphorylation. Cancer Res. 56:4192-4196, 1996.
22. Constantinou AI, Mehta RG, Vaughan A. Inhibition of N-methyl-N-nitrosourea-Induced Mammary Tumors in Rats by the Soybean Isoflavones. Anticancer Res.,16: 3293-3298, 1996.
23. Mehta RG, Moriaty RM, Mehta RR, Penmasta R, Lazzaro G, Constantinou AI, Knutson JC, Guo L. Prevention of preneoplastic mammary lesion development by a novel vitamin D analog 1alpha(hydroxy)vitamin D5. J. Natl. Cancer Inst., 89: 212-218, 1997.
24. Krygier A, Murley JS, Mehta RR, Constantinou AI. Induction of human adenocarcinoma cell differentiation by the phytoestrogen genistein is independent to its antiestrogenic function . Int J. Oncol. 10:753-757, 1997.
25. Constantinou AI, Runyan C, Grdina D, Murley J. Apoptosis and cell cycle delay in G2-M phase introduced by the phytoestrogen genistein. Phytomedicine (suplement I) 3: 124-125, 1997.
26. Hesser P, Larsen PE, Constantinou AI, Schram KH, Weber JM. Isolation of isoflavones from soy-based fermentations of the erythromycin-producing bacterium Saccharopolyspora erythrea. Appl. Microbiol. Biotechnol 47: 398-404, 1997.
27. Khodarev NA, Narayanna A, Constantinou AI, Vaughan ATM. Topologically constrained domains of supercoiled DNA in eukaryotic cells. DNA and Cell Biology 16: 1051-1058, 1997.
28. Murley JS, Constantinou AI, Grdina DJ. WR-1065, an active metabolite of the cytoprotector amifostine, affects phosporylation of topoisomerase II ? leading to changes in enzyme activity and cell cycle progression in CHO AA8 cells. Cell Proliferation, 30: 283-294, 1997.
29. Krygier A, Mehta RR, Constantinou AI. Genistein induces maturation of human breast cancer cells and prevents tumor growth in nude mice. Am. J. Clin. Nutr, 68 (supl):1426S-30S,1998.
30. Constantinou AI, Kamath N, Murley JA. Genistein inactivates bcl-2, delays G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells. Eur. J. Cancer, 34: 1927-1934, 1998.
31. Boddie AW, Constantinou AI, Williams C, Reed A. Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cell line. Br. J. Cancer, 77:1395-1404, 1998.
32. Aoyama M, Grabowski D, Dubyak G, Constantinou AI, Rybicki L, Bukowski R, Ganapathi M, Hickson I, Ganapathi R. Attenuation of drug stimulated DNA cleavage complex formation and cytotoxicity is associated with alterations in phosphorylation of topoisomerase II alpha. Biochemical Journal, 15:336:723-733, 1998.
33. Xiaoyig Xu, Wang Y, Constantinou AI, Stacewicz-Sapuntzakis M, Bowen P, van Breemen R. Solubilization and stabilization of carotenoids using micelles: Delivery of lycopene to cells in culture. Lipids, 34: 1031-1036, 1999.
34. Constantinou AI, Salti G. Application of Topoisomerase Assays in the Evaluation of Natural Products as Antitumor Agents. Journal of Medicinal Food, 2: 149-153, 1999.35. Salti GI, Das Gupta TK, Constantinou AI. A novel use for the comet assay; detection of topisomerase II inhibitors. Anticancer Res., 20: 3189-3193, 2000.
36. Chen Y, Liu X, Pisha E, Constantinou AI, Hua Y, Shen L, van Breemen RB, Elguindi EC, Blond, SY, Zhang F, Bolton JL. A metabolite of equine estrogens, 4-hydroxyequilenin, induces DNA damage and apoptosis in breast cancer cell lines. Chem. Res. Toxicol.,13: 342-50, 2000.
37. Salti GI, Mehta RJ, Das Gupta TK, Boddie AW, Grewal S, Constantinou AI. Genistein-induced DNA breaks in HT-29 colon cancer cells are mediated by topoisomerase II as detected by the comet assay. Eur. J. Cancer, 36: 796-802, 2000.
38. Cho KH, Pezzuto JM, Bolton JL, Steele VE, Kelloff, GJ, Lee SK, Constantinou AI. Selection of Cancer Chemopreventive Agents Based on Inhibition of Topoisomerase II Activity. Eur. J. Cancer 36: 2146-2156, 2000.
39. Pisha E, Lui X, Constantinou AI, Bolton J. Evidence that a metabolite of equine estrogens, 4-Hydroxyequilenin, induces cellular transformation in vitro. Chem. Res. Toxicol. 14:82-90, 2001.
40. Salti G, Kichina J, Das Gupta T, Uddin S, Bradescu L, Pezzuto J, Mehta R, Constantinou AI. Betulinic acid reduces UV-C-induced DNA breakage in congenital melanocytic neval cells: evidence for potential role as a chemopreventive agent. Melanoma Res. 11:99-104, 2001.
41. Liu J, Burdette JE, Xu H, Gu C, Bhat K, Booth N, Constantinou AI, van Breemen RB, Pezzuto JM, Fong HHS, Farnsworth NR, Bolton JL. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agr. Food Chem. 49: 2472-2479, 2001.
42. Constantinou AI, Lantvit D, Hawthorn M, Xu X, van Breemen R, Pezzuto J. Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats. Nutrition and Cancer 41: 75-81, 2001.
43. Burdette J, Liu J, Lantvit D, Lim E, Booth N, Bhat KPL, van Breemen RB, Constantinou AI, Pezzuto JM, Farnsworth NR, Bolton JL. In vivo estrogenic effects of Trifolium pratense (red clover) in ovariectomized Sprague-Dawley rats. J. Nutr. 132: 27-30, 2002.
44. Constantinou AI, Rossi H, Lantvit D, Hawthorn M, Xu X, Nho C-W, Jefferey EH, Christov K, van Breemen R, Pezzuto J. Soy protein isolate prevents chemically induced rat mammary tumors. Pharmaceutical Biology 40: 24-34, 2002.
45. Block KI, Constantinou A, Hilakivi-Clarke L, Hughes C, Tripathy D, Tice JA. Point-counterpoint: soy intake for breast cancer patients. Integr Cancer Ther, 1: 90-100, 2002.
46. Burdette JE, Chen SN, Lu ZZ, Xu H, White BE, Fabricant DS, Liu J, Fong HH, Farnsworth NR., Constantinou AI, Van Breemen RB, Pezzuto JM,Bolton JL. Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: bioassay-directed isolation and characterization of active principles. J Agric Food Chem, 50: 7022-7028, 2002.
47. Constantinou AI, Husband, A. Phenoxodiol (2H-1-benzopyran-7-0,1,3-(4-hydroxyphenyl)), a novel isoflavone derivative, inhibits DNA topoisomerase II by stabilizing the cleavable complex. Anticancer Res, 22: 2581-2585, 2002.
48. Xu, H., Fabricant, D. S., Piersen, C. E., Bolton, J. L., Pezzuto, J. M., Fong, H., Totura, S., Farnsworth, N. R., and Constantinou, A. I. A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for women's health. Phytomedicine, 9: 757-762, 2002.
49. Constantinou, A. I., Mehta, R., and Husband A. Phenoxodiol, a novel isoflavone derivative, inhibits dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. Eur J Cancer, 39: 1012-1018, 2003.50. Gentile MS, Vasu C, Green A, Murillo G, Das Gupta TK, Constantinou AI, Prabhakar BS, Salti GI. Targeting colon cancer cells with genistein-17.1A immunoconjugate. Int J Oncol, 22: 955-959, 2003.
51. Tonetti DA, Rubenstein R, DeLeon M, Zhao H, Pappas SG, Bentrem DJ, Chen B, Constantinou A, Jordan CV. Stable transfection of an estrogen receptor beta cDNA isoform into MDA-MB-231 breast cancer cells. J Steroid Biochem Mol Biol, 87: 47-55, 2003.
52. Guo JY, Li X, Browning JD Jr, Rottinghaus GE, Lubahn DB, Constantinou A, Bennink M, MacDonald RS, Dietary soy isoflavones and estrone protect ovariectomized ERalphaKO and wild-type mice from carcinogen-induced colon cancer. J Nutr, 134: 179-182, 2004.
53. Punj V, Bhattacharyya S, Saint-Dic D, Vasu C, Cunningham EA, Graves J, Yamada T, Constantinou AI, Christov K, White B, Li G, Majumdar D, Chakrabarty AM, Das Gupta TK. Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer. Oncogene, 23: 2367-2378, 2004.
54. Murillo G, Choi, J, Pan O, Constantinou A, Mehta R. Garbanzo bean flour is as effective as soy bean flour in suppressing the formation of aberrant crypt in the colons of CF-1 mice. Anticancer Res. 24:3049-55 2004.
55. Constantinou AI, White BEP, Tonetti D, Yang Y, Liang W, Li W, van Breemen RB. The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary tumors. European J Cancer, 41: 647-654, 2005
56. Tonetti DA, Zhang Y, Zhao H, Lim SB, Constantinou AI. The effect of the phytoestrogens genistein, daidzein, and equol on the growth of tamoxifen-resistant T47D/PKC alpha. Nutr Cancer 58:222-229, 2007
57. Constantinou C, Papas A and Constantinou AI. Vitamin E and Cancer: An insight into the anticancer activities of vitamin E isomers and analogues. Int J Cancer, 123:739-52, 2008.
58. Georgaki S, Skopeliti M, Tsiatas M, Nicolaou KA, Husband Al, Bamias A, Constantinou AI, Tsitsilonis OE. Phenoxodiol, an anticancer isoflavene, induces immunomodulatory effects in vitro and in vivo. J Cell Mol Med. 20: 1-10, 2009.
59. Batsi C, Markopoulou S, Kontargiris E, Charalambous C, Thomas C, Christoforidis S, Kanavaros P, Constantinou AI, Marcu KB, Kolettas E. Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27(Kip1)-dependent G1/S cell cycle arrest in conjunction with NF-kappaB activation. Biochem Pharmacol. 78:33-44, 2009.
60. Constantinou C, Papas KA, Constantinou AI. Caspase-independent pathways of programmed cell death: the unraveling of new targets of cancer therapy? Curr Cancer Drug Targets 9:717-28, 2009.
61. Constantinou C, Hyatt JA, Vraka PS, Papas A, Papas KA, Neophytou C, Hadjivassiliou V, Constantinou AI. Induction of caspase-independent programmed cell death by vitamin E natural homologs and synthetic derivatives. Nutr Cancer: 61:864-74, 2009.
62. Constantinou C, Neophytou CM, Vraka P, Hyatt JA, Papas KA, Constantinou AI. Induction of DNA Damage and Caspase-Independent Programmed Cell Death by Vitamin E. Nutr Cancer. 64:136-152 2012.
63. Nicolaou KA, Liapis V, Evdokiou A, Constantinou C, Magiatis P, Skaltsounis AL, Koumas L, Costeas PA, Constantinou AI. Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells. Biochem Biophys Res Commun. 425:76-82. 2012.
64. Odiatou EM, Skaltsounis AL, Constantinou AI. Identification of the factors responsible for the in vitro pro-oxidant and cytotoxic activities of the olive polyphenols oleuropein and hydroxytyrosol. Cancer Lett. 330:113-21, 2013. 
65. Charalambous C, Pitta C and Constantinou AI. Equol enhances tamoxifen’s antitumor activity by induction of caspace-mediated apoptosis. BMC Cancer. 13:238-247, 2013.
66. Pitta C, Papagiorges P., Constantinou AI. Combination treatment with TSA and 5-aza-dc restores response to tamoxifen in tamoxifen resistant ER-β negative breast cancer cells. Cancer Lett. 337: 167-176, 2013
67. Cretu E, Karonen M, Salminen JP, Mircea C, Trifan A, Charalambous C, Constantinou AI, Miron A. In vitro study of the antioxidant activity of a polyphenol-rich extract from Pinus brutia bark and its fractions. J Med Food16:984-91, 2013
68. Neophytou CM, Constantinou C, Papageorgis P, Constantinou AI. D-alpha-tocopheryl polyethylene glycol succinate (TPGS) induces cell cycle arrest and apoptosis selectively in Survivin-overexpressing breast cancer cells. Biochem Pharmacology, 2014 (in press).
69. Miron A, Olymbiou C, Charalambous C, Neophytou C, Salminen JP, Karonen  M, Constantinou AI. Chemical composition, antioxidant and antiproliferative  activity of a polyphenol-rich fraction from Pinus sylvestris L. Bark. (in press).