• 1
    McGuire W.P., Hoskins W.J., Brady M.F., Kucera P.R., Partridge E.E., Look K.Y., Clarke-Pearson D.L., Davidson M. (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med;334:16.
  • 2
    International Collaborative Ovarian Neoplasm Group (2002) Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet;360:505515.
  • 3
    Creasman W.T., Morrow C.P., Bundy B.N., Homesley H.D., Graham J.E., Heller P.B. (1987) Surgical pathologic spread patterns of endometrial cancer. A gynecologic Oncology Group Study. Cancer;60:20352041.
  • 4
    Thigpen J.T., Brady M.F., Homesley H.D., Malfetano J., DuBeshter B., Burger R.A., Liao S. (2004) Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol;22:39023908.
  • 5
    Hoskins P.J., Swenerton K.D., Pike J.A., Wong F., Lim P., Acquino-Parsons C., Lee N. (2001) Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol;19:40484053.
  • 6
    Hecht S.S. (2004) Chemoprevention by isothiocyanates. In: Kelloff G., Hawk E.T., Sigman C.C., editors. Promising Cancer Chemopreventive Agents, Vol 1: Cancer Chemopreventive Agents. Totowa, NJ: Humana Press; p. 2135.
  • 7
    Conaway C.C., Wang C.X., Pittman B., Yang Y.M., Schwartz J.E., Tian D., McIntee E.J., Hecht S.S., Chung F.L. (2005) Phenethyl isothiocyanate and sulforaphane and their N-acetylcysteine conjugates inhibit malignant progression of lung adenomas induced by tobacco carcinogens in A/J mice. Cancer Res;65:85488557.
  • 8
    Conaway C.C., Yang Y., Lunk F.C. (2002) Isothiocynates as chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr Drug Metab;3:233255.
  • 9
    Tang L., Li G., Song L., Zhang Y. (2006) The principal urinary metabolites of dietary isothiocyanates, N-acetylcysteine conjugates, elicit the same anti-proliferative response as their parent compounds in human bladder cancer cells. Anticancer Drugs;17:297305.
  • 10
    Chung F.L., Conaway C.C., Rao C.V., Reddy B.S. (2002) Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis;21:22872291.
  • 11
    Kalkunte S., Swamy N., Dizon D.S., Singh R., Granai C.O., Brard L. (2006) Phenethyl isothiocyanate (PEITC) inhibits growth of ovarian cancer cells by inducing apoptosis: role of caspase and MAPK activation. Gynecol Oncol;103:261270.
  • 12
    Kalkunte S., Swamy N., Dizon D.S., Granai C.O., Brard L. (2006) Benzyl Isothiocyanate (BITC) induces apoptosis in ovarian carcinoma. J Exp Ther Oncol;5:287300.
  • 13
    Singh S.V., Herman-Antosiewicz A., Singh A.V., Lew K.L., Srivastava S.K., Kamath R., Brown K.D., Zhang L., Baskaran R. (2004) Sulforaphane-induced G2/M phase cell-cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle. J Biol Chem;279:2581325822.
  • 14
    Jackson S.J., Singletary K.W., Venema R.C. (2007) Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. Vascul Pharmacol;46:7784.
  • 15
    Xiao D., Singh S.V. (2007) Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res;67:22392246.
  • 16
    Barecki R.M., Wang E.J., Johnson W.W. (2003) Quantitative evaluation of isothiocyanates as substrates and inhibitors of P-glycoprotein. J Pharm Pharmacol;55:12511257.
  • 17
    Tseng E., Kamath A., Morris M.E. (2002) Effect of organic isothiocyanates on the P-glycoprotein- and MRP1-mediated transport of daunomycin and vinblastine. Pharm Res;19:15091515.
  • 18
    Yang Y.M., Conaway C.C., Chiao J.W., Wang C.X., Amin S., Whysner J., Dai W., Reinhardt J., Chung F.L. (2002) Inhibition of benzo(a)pyrene-induced lung tumorigenesis in A/J mice by dietary N-acetylcysteine conjugates of benzyl and phenethyl isothiocyanates during the postinitiation phase is associated with activation of mitogen-activated protein kinases and p53 activity and induction of apoptosis. Cancer Res;62:27.
  • 19
    Chiao J.W., Wu H., Ramaswamy G., Conaway C.C., Chung F.L., Wang L., Liu D. (2004) Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis;25:14031408.
  • 20
    Hwang E.S., Lee H.J. (2006) Allyl isothiocyanate and its N-acetylcysteine conjugate suppress metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in SK-Hep 1 human hepatoma cells. Exp Biol Med;231:421430.
  • 21
    Singh R.K., Lange T.S., Kim K., Zou Y., Lieb C., Sholler G.L., Brard L. (2007) Effect of indole ethyl isothiocyanates on proliferation, apoptosis and MAPK signaling in neuroblastoma cell lines. Bioorg Med Chem Lett;17:58465852.
  • 22
    Brard L., Singh R.K., Kim K.K., Lange T.S., Sholler G.S. (2009) Induction of cytotoxicity, apoptosis and cell-cycle arrest by 1-t-butyl carbamoyl, 7-methyl-indole-3-ethyl isothiocyanate (NB7M) in nervous system cancer cells. Drug Des Devel Ther;2:6169.
  • 23
    Singh R.K., Lange T.S., Kim K.K., Singh A.P., Vorsa N., Brard L. (2008) Isothiocyanate NB7M causes selective cytotoxicity, pro-apoptotic signaling and cell-cycle regression in ovarian cancer cells. Br J Cancer;99:18231831.
  • 24
    Singh R.K., Lange T.S., Shaw S., Kim K.K., Brard L. (2008) A novel Indole Ethyl Isothiocyanate (7Me-IEITC) with anti-proliferative and pro-apoptotic effects on platinum-resistant ovarian cancer cells. Gyn Onc;109:240249.
  • 25
    Bodo J., Hunakova L., Kvasnicka P., Jakubikova J., Duraj J., Kasparkova J., Sedlak J. (2006) Sensitisation for cisplatin-induced apoptosis by isothiocyanate E-4IB leads to signalling pathways alterations. Br J Cancer;95:13481353.
  • 26
    Prelog V., Seiwerth R. (1941) Über die Synthese des Adamantans. Berichte;74:16441648.
  • 27
    Van der Schyf C.J., Geldenhuys W.J. (2009) Polycyclic compounds: ideal drug scaffolds for the design of multiple mechanism drugs? Neurotherapeutics;6:175186.
  • 28
    Pfahl M. (2004) Apoptosis inducing adamantyl derivatives and their usage as anti-cancer agents, especially for cervical cancers and dysplasias. United States Patent 6825226
  • 29
    Farhana L., Dawson M.I., Huang Y., Zhang Y., Rishi A.K., Reddy K.B., Freeman R.S., Fontana J.A. (2004) Apoptosis signaling by the novel compound 3-Cl-AHPC involves increased EGFR proteolysis and accompanying decreased phosphatidylinositol 3-kinase and AKT kinase activities. Oncogene;23:18741884.
  • 30
    Dawson M.I., Xia Z., Liu G., Ye M., Fontana J.A., Farhana L., Patel B.B. et al. (2007) An adamantyl-substituted retinoid-derived molecule that inhibits cancer cell growth and angiogenesis by inducing apoptosis and binds to small heterodimer partner nuclear receptor: effects of modifying its carboxylate group on apoptosis, proliferation, and protein-tyrosine phosphatase activity. J Med Chem;50:26222639.
  • 31
    Lange T.S., Kim K.K., Singh R.K., Strongin R.M., McCourt C.K., Brard L. (2008) Iron(III)-salophene: an metallo-organic compound with selective cytotoxic and anti-proliferative properties in platinum-resistant ovarian cancer cells. PLoS ONE;3:e2303.
  • 32
    Lange T.S., Singh R.K., Kim K.K., Zou Y., Kalkunte S.S., Sholler G.L., Swamy N., Brard L. (2007) Anti-proliferative and pro-apoptotic properties of 3-Bromoacetoxy Calcidiol (B3CD) in high-risk neuroblastoma. Chem Biol Drug Des;70:302310.
  • 33
    Li J., Dowdy S., Tipton T., Podratz K., Lu W.G., Xie X., Jiang S.W. (2009) HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn;9:555566.
  • 34
    Moore R.G., McMeekin D.S., Brown A.K., DiSilvestro P., Miller M.C., Allard W.J., Gajewski W., Kurman R., Bast R.C. Jr, Skates S.J. (2009) A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol;112:4046.
  • 35
    Moore R.G., Brown A.K., Miller M.C., Badgwell D., Lu Z., Allard W.J., Granai C.O., Bast R.C. Jr, Lu K. (2008) Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus. Gynecol Oncol;110:196201.
  • 36
    Witschi H., Espiritu I., Yu M., Willits N.H. (1998) The effects of phenethyl isothiocyanate, N-acetylcysteine and green tea on tobacco smoke-induced lung tumors in strain A/J mice. Carcinogenesis;19:17891794.
  • 37
    Masutomi N., Toyoda K., Shibutani M., Niho N., Uneyama C., Takahashi N., Hirose M. (2001) Toxic effects of benzyl and allyl isothiocyanates and benzyl-isoform specific metabolites in the urinary bladder after a single intravesical application to rats. Toxicol Pathol;29:617622.
  • 38
    Hartwell L.H., Kastan M.B. (1994) Cell-cycle control and cancer. Science;266:18211828.
  • 39
    Gladden A.B., Diehl J.A. (2003) Cell-cycle progression without cyclin E/CDK2: breaking down the walls of dogma. Cancer Cell;4:160162.
  • 40
    Aggarwal P., Lessie M.D., Lin D.I., Pontano L., Gladden A.B., Nuskey B., Goradia A., Wasik M.A., Klein-Szanto A.J., Rustgi A.K., Bassing C.H., Diehl J.A. (2007) Nuclear accumulation of cyclin D1 during S phase inhibits Cul4-dependent Cdt1 proteolysis and triggers p53-dependent DNA rereplication. Genes Dev;21:29082922.
  • 41
    Pines J. (1999) Four-dimensional control of the cell-cycle. Nat Cell Biol;1:7379.
  • 42
    Stillman B. (1996) Cell-cycle control of DNA replication. Science;274:16591664.
  • 43
    Shapiro G.I., Harper J.W. (1999) Anticancer drug targets: cell-cycle and checkpoint control. J Clin Invest;104:16451653.
  • 44
    Mazumder S., DuPree E.L., Almasan A. (2004) A dual role of cyclin E in cell proliferation and apoptosis may provide a target for cancer therapy. Curr Cancer Drug Targets;4:6575.
  • 45
    Zhou H.Y., Pon Y.L., Wong A.S. (2007) Synergistic effects of epidermal growth factor and hepatocyte growth factor on human ovarian cancer cell invasion and migration: role of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. Endocrinology;148:51955208.
  • 46
    Chauhan S.C., Vannatta K., Ebeling M.C., Vinayek N., Watanabe A., Pandey K.K., Bell M.C., Koch M.D., Aburatani H., Lio Y., Jaggi M. (2009) Expression and functions of transmembrane mucin MUC13 in ovarian cancer. Cancer Res;69:765774.
  • 47
    Mansouri A., Ridgway L.D., Korapati A.L., Zhang Q., Tian L., Wang Y., Siddik Z.H., Mills G.B., Claret F.X. (2003) Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells. J Biol Chem;278:1924519256.
  • 48
    Benedetti V., Perego P., Luca Beretta G., Corna E., Tinelli S., Righetti S.C., Leone R., Apostoli P., Lanzi C., Zunino F. (2008) Modulation of survival pathways in ovarian carcinoma cell lines resistant to platinum compounds. Mol Cancer Ther;7:679687.
  • 49
    Albitar L., Pickett G., Morgan M., Wilken J.A., Maihle N.J., Leslie K.K. (2010) EGFR isoforms and gene regulation in human endometrial cancer cells. Mol Cancer;9:166179.
  • 50
    Waris G., Ahsan H.J. (2006) Reactive oxygen species: role in the development of cancer and various chronic conditions. Carcinogenesis;5:18.
  • 51
    Gupte A., Mumper R.J. (2009) Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treat Rev;35:3246.
  • 52
    Hileman E.O., Liu J., Albitar M., Keating M.J., Huang P. (2004) Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol;53:209219.
  • 53
    Trachootham D., Alexandre J., Huang P. (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov;8:579591.
  • 54
    Kim K.K., Singh R.K., Strongin R.M., Moore R.G., Brard L., Lange T.S. (2011) Organometallic Iron(III)-salophene exerts cytotoxic properties in neuroblastoma cells via MAPK activation and ROS generation. PLoS ONE;6:e19049.
  • 55
    Horan T.C., Zompa M.A., Seto C.T., Kim K.K., Moore R.G., Lange T.S. (2011) Description of the cytotoxic effect of a novel drug abietyl-isothiocyanate on endometrial cancer cell lines. Invest New Drugs; DOI: 10.1007/s10637-011-9728-z.
  • 56
    Osone S., Hosoi H., Kuwahara Y., Matsumoto Y., Lehara T., Sugimoto T. (2004) Fenretinide induces sustained-activation of JNK/p38 MAPK and apoptosis in a reactive oxygen species-dependent manner in neuroblastoma cells. Int J Cancer;112:219224.
  • 57
    Kang Y.H., Lee S.J. (2008) The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells. J Cell Physiol;217:2333.