Relative impact of 3- and 5-hydroxyl groups of cytosporone B on cancer cell viability.

A novel and the shortest route, thus far, for preparing cytosporone B (Csn-B) is reported. Csn-B and two analogs were used to probe the importance of hydroxyl groups at the 3- and 5-positions of the Csn-B benzene ring in inhibiting the viability of human H460 lung cancer and LNCaP prostate cancer cells, inducing H460 cell apoptosis, and interacting with the NR4A1 (TR3) ligand-binding domain (LBD). These studies indicate that Csn-B and 5-Me-Csn-B, having a phenolic hydroxyl at the 3-position of their aromatic rings, had similar activities in inhibiting cancer cell viability and in inducing apoptosis, whereas 3,5-(Me)2-Csn-B was unable to do so. These results are in agreement with ligand-binding experiments showing that the interaction with the NR4A1 LBD required the presence of the 3-hydroxyl group.

[1]  I. H. Koumakpayi,et al.  ErbB2/Her‐2 regulates the expression of Akt2 in prostate cancer cells , 2012, The Prostate.

[2]  S. Safe,et al.  Targeting NR4A1 (TR3) in cancer cells and tumors , 2011, Expert opinion on therapeutic targets.

[3]  Y. Wang,et al.  A unique pharmacophore for activation of the nuclear orphan receptor Nur77 in vivo and in vitro. , 2010, Cancer research.

[4]  J. Ohshita,et al.  An Aryne Route to Cytosporone B and Phomopsin C , 2010 .

[5]  S. Safe,et al.  Enhancement of Docetaxel Anticancer Activity by a Novel Diindolylmethane Compound in Human Non–Small Cell Lung Cancer , 2009, Clinical Cancer Research.

[6]  B. Weimer,et al.  Cytosporone B is an agonist for nuclear orphan receptor Nur77. , 2008, Nature chemical biology.

[7]  B. Chenard,et al.  An efficient preparation of beta-aryl-beta-ketophosphonates by the TFAA/H3PO4-mediated acylation of arenes with phosphonoacetic acids. , 2008, The Journal of organic chemistry.

[8]  H. Shiina,et al.  Rationale and clinical implication of combined chemotherapy with cisplatin and oestrogen in prostate cancer: primary evidence based on methylation analysis of oestrogen receptor‐α , 2007, BJU international.

[9]  John Calvin Reed,et al.  Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myeloma. , 2007, Blood.

[10]  Sudhakar Chintharlapalli,et al.  1,1-Bis(3′-Indolyl)-1-(p-substitutedphenyl)methanes Inhibit Growth, Induce Apoptosis, and Decrease the Androgen Receptor in LNCaP Prostate Cancer Cells through Peroxisome Proliferator-Activated Receptor γ-Independent Pathways , 2007, Molecular Pharmacology.

[11]  R. Paulsen,et al.  Three related brain nuclear receptors, NGFI-B, Nurr1, and NOR-1, as transcriptional activators , 2007, Journal of Molecular Neuroscience.

[12]  John Calvin Reed,et al.  Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt , 2006, Oncogene.

[13]  C. Le Page,et al.  Independent role of phosphoinositol‐3‐kinase (PI3K) and casein kinase II (CK‐2) in EGFR and Her‐2‐mediated constitutive NF‐kappaB activation in prostate cancer cells , 2005, The Prostate.

[14]  K. Yoon,et al.  Activation of Nur77 by Selected 1,1-Bis(3′-indolyl)-1-(p-substituted phenyl)methanes Induces Apoptosis through Nuclear Pathways* , 2005, Journal of Biological Chemistry.

[15]  D. Moras,et al.  Structural Basis for the Cell-specific Activities of the NGFI-B and the Nurr1 Ligand-binding Domain* , 2005, Journal of Biological Chemistry.

[16]  M. Dawson,et al.  These include: , 1993 .

[17]  M. Dawson,et al.  Mitogenic Effect of Orphan Receptor TR3 and Its Regulation by MEKK1 in Lung Cancer Cells , 2003, Molecular and Cellular Biology.

[18]  Qiao Wu,et al.  Dual roles of Nur77 in selective regulation of apoptosis and cell cycle by TPA and ATRA in gastric cancer cells. , 2002, Carcinogenesis.

[19]  D. Moras,et al.  Molecular recognition of agonist ligands by RXRs. , 2002, Molecular endocrinology.

[20]  T. Steiner.  The hydrogen bond in the solid state. , 2002, Angewandte Chemie.

[21]  J. Cheville,et al.  PTEN Induces Chemosensitivity in PTEN-mutated Prostate Cancer Cells by Suppression of Bcl-2 Expression* , 2001, The Journal of Biological Chemistry.

[22]  M. Dawson,et al.  Apoptosis induction in cancer cells by a novel analogue of 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid lacking retinoid receptor transcriptional activation activity. , 2001, Cancer research.

[23]  J. Clardy,et al.  Cytoskyrins A and B, new BIA active bisanthraquinones isolated from an endophytic fungus. , 2000, Organic letters.

[24]  D. Ross,et al.  A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor quinones: identification of a new aziridinylbenzoquinone, RH1, as a NQO1-directed antitumor agent. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  Timothy P. Smyth and,et al.  Toward a Clean Alternative to Friedel−Crafts Acylation: In Situ Formation, Observation, and Reaction of an Acyl Bis(trifluoroacetyl)phosphate and Related Structures , 1998 .

[26]  H. Uemura,et al.  Antisense TR3 orphan receptor can increase prostate cancer cell viability with etoposide treatment. , 1998, Endocrinology.

[27]  P. Chambon,et al.  Conformational adaptation of agonists to the human nuclear receptor RARγ , 1998, Nature Structural Biology.

[28]  Zong-hou Shen,et al.  Restoration of the p16 gene is related to increased radiosensitivity of p16-deficient lung adenocarcinoma cell lines , 1998, Journal of Cancer Research and Clinical Oncology.

[29]  J. Drouin,et al.  Novel dimeric Nur77 signaling mechanism in endocrine and lymphoid cells , 1997, Molecular and cellular biology.

[30]  K. Umesono,et al.  Unique response pathways are established by allosteric interactions among nuclear hormone receptors , 1995, Cell.

[31]  T. Perlmann,et al.  A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. , 1995, Genes & development.

[32]  C. Young,et al.  Tumor-promoting phorbol ester-induced cell death and gene expression in a human prostate adenocarcinoma cell line. , 1994, Oncology research.

[33]  N. Davidson,et al.  Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. , 1993, Cancer research.

[34]  J. Milbrandt,et al.  Domains regulating transcriptional activity of the inducible orphan receptor NGFI-B. , 1992, The Journal of biological chemistry.

[35]  G. Jenster,et al.  A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. , 1990, Biochemical and biophysical research communications.

[36]  A. Gazdar,et al.  Inhibition of N-diethylnitrosamine metabolism by human lung cancer cell lines with features of well differentiated pulmonary endocrine cells. , 1987, Biochemical pharmacology.

[37]  G. Murphy,et al.  LNCaP model of human prostatic carcinoma. , 1983, Cancer research.

[38]  W. Schäfer,et al.  Selektive Ätherspaltung von 4‐Hydroxy‐methoxy‐chinolincarbonsäureestern , 1966 .