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Graduate Program in Pharmaceutical Science |
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Faculty Profiles
Current Interests: Prevention of Diseases including Cancer by Dietary Phytochemicals (signaling, gene expression and in vivo pharmacological effects); Pharmacogenomics and toxicogenomics of cancer chemopreventive compounds, MAP Kinases / Nrf2 transcription factor-mediated gene expression, and pharmacokinetics and pharmacodyanmics of drug action. Evolutionarily, animals
have been ingesting plants. This “animal-plant” warfare has resulted in an
elaborated system of detoxification and defense mechanisms evolved by animals
including humans. Mammalian including human cells respond to these dietary phytochemicals by “non-classical receptor sensing”
mechanism of electrophilic chemical-stress typified
by ‘thiol modulated” cellular signaling events
leading to gene expression of either pharmacologically beneficial effects,
but some time also unwanted cytotoxicity. Our
laboratory has been studying two groups of dietary phytochemical
cancer chemopreventive compounds (isothiocyanates and polyphenols),
which are effective against chemical-induced as well as genetically induced
animal carcinogenesis models. These compounds typically generate “cellular
stress” and modulate gene expression of Phase II detoxifying/antioxidant
enzymes GST, QR, HO-1 and GCS via the Keap1-Nrf2/ARE signaling pathway. However, using Nrf2 -/- mice coupled with Affymetrix microarray analyses, other category of genes
including the Phase I drug metabolism enzyme cytochrome
P450s, Phase III transporters, ubiquitination,
electron transport, cell growth and apoptosis, cell adhesion, kinases, phosphotases and
transcription factors modulated by these compounds appeared to be
Nrf2-dependent, at least in normal tissues, leading to the overall cellular
protective effects against oxidative stress or carcinogenic damages.
Importantly, in tumor tissues, these phytochemicals
appear to simultaneously modulate differentially over-expressed growth or
inflammatory signaling molecules such as the MAPK, IKK/NF-kappa-B signaling
pathways culminating the apoptotic or autophagic
cell death of tumor or inflammatory cells. The differential signaling/gene
expression between “normal” versus “abnormal” cells would dictate the varied
biological responses and pharmacological effects in vivo elicited by these
dietary compounds. The studies of these signaling pathways coupled with
microarray or proteomic approaches may yield important insights into the
potential beneficial health effects of naturally occurring dietary phytochemicals in human. The research of my
laboratory is to study two important cellular signaling pathways, the mitogen-activated protein kinases
(MAPKs) and the caspases
pathways activated by these compounds as well as environmental agents and
chemotherapeutic drugs. One of the downstream targets that are modulated by chemopreventive agents-induced MAPK signaling is the bZIP transcription factors Nrf2/Maf which induce cellular
defensive enzymes via the antioxidant response element (ARE). Our lab had
shown that various MAPK proteins modulate the transcriptional activity of
Nrf2 on ARE-luciferase reporter gene leading gene
to expression of cellular defense enzymes such as heme-oxygenase-1 and Phase
II drug metabolizing enzymes. Our approach to investigate various chemopreventive agents are to combine biochemical and molecular biology in cell cultures combined with appropriate in vivo animal models for human cancers of colon and prostate. Ongoing projects focus on: (i) Chemoprevention of cancer: Preclinical and clinical studies of chemopreventive agents; (ii) Drug metabolism: Biochemistry, pharmacology and regulation of gene expression of drug metabolizing enzymes (cytochrome P450s and phase II enzymes) in relationship to carcinogenesis and chemoprevention; (iii) Cellular signal transduction: MAPK; ERK, JNK, p38 in regulation of gene expression in cell survival and apoptosis; (iv) Apoptosis: Role of caspases, TRAIL and death receptors (DRs) in apoptosis; (v) Pharmacogenomics and toxicogenomics; (vi) Pharmacokinetics, and pharmacodynamics of anti-cancer drugs (preventive and chemotherapeutics) and environmental agents; and (vii) Prostate cancer: Biology, signaling, prevention and therapy. Education: Postdoctoral Training, 1991, National Institutes of Health Ph.D. 1989, Pharmaceutics &
Pharmacokinetics, State B.S. 1983, Pharmacy, Member of the Editorial Board and Study Section: Editor; Pharmaceutical Research (2005-present) Pharmaceutical Research (2001-present) Archives of Pharmacal Research (1999-present) Biopharmaceutics and Drug Disposition (2005-present) NIH Chemical-Dietary (CDP) Study Section (2005-2009) Publications (Representative): 2008 Zheng, X., Chang, R.L., Cui, X.X., Khor, T.O., Huang, M.T., Prawan, A., Liu, Y., Hao, X., Yu, S., Cheung, K.L., Chan, J.Y., Reddy, B.S., Yang, C.S., and Kong, A.N.T. Nrf2-deficient mice have an increased susceptibility to azoxymethane/dextran sulfate sodium-induced colitis- associated colorectal carcinogenesis. Cancer Prevention Research (first issue), 1:xxx, 2008. Nair, S., Hebbar, V., Shen, S., Gopalakrishnan, A., Khor, T.O., Yu, S., Xu, C., and Kong, A.N.T. Synergistic effects of a combination of dietary factors sulforaphane and (-) epigallocatechin-3-gallate in HT-29 AP-1 human colon carcinoma cells. Pharmaceutical Research 2008 Feb;25(2):387-99, 2008. Keum, Y.-S., Chang, P.P-J., Yuan, X., Hu, L., and Kong, A.-N.T. 3-morpholinopropyl isothiocyanate is a novel synthetic isothiocyanate that strongly induces the antioxidant response element (ARE)-dependent phase II detoxifying enzymes by modulating multiple signaling pathways. Carcinogenesis. Mar;29(3):594-9, 2008. Van Berkel, G.J., Kertesz, V., Koeplinger, K.A., Vavrek, M., and Kong, A.N.T. Liquid Microjunction Surface Sampling Probe Electrospray Mass Spectrometry for Detection of Drugs and Metabolites in Thin Tissue Sections. J Mass Spectrom. 2008 Apr;43(4):500-8. Gopalakrishnan, A., and Kong, A.N.T. Anticarcinogenesis by dietary phytochemicals: Cytoprotection by Nrf2 in normal cells and cytotoxicity by modulation of transcription factors NF-κB and AP-1 in abnormal cancer cells. Food Chemical Toxicology Apr;46(4):1257-70, 2008. Prawan, A., Keum, Y.-S., Khor, T.O., Yu, S., Nair, S., Li, W., Hu, L. and Kong, A.N.T. Structural Influence of Isothiocyanates on the Antioxidant Response Element (ARE)-mediated Heme Oxygenase-1 (HO-1) Expression in HepG2 Cells. Pharmaceutical Research Apr;25(4):836-44, 2008. Khor TO, Cheung WK, Prawan A, Reddy BS, and Kong, A.-N.T. Chemoprevention of familial adenomatous polyposis in ApcMin/+ mice by phenethyl isothiocyanate (PEITC). Mol Carcinog. May;47(5):321-5, 2008. In press or Acceptable for publicationGopalakrishnan, A., Khor, T.O., Nair, S., Lin, W., Yu, S., Jain, M.R., Chan, J.Y., and Kong, A.N.T. Pharmacogenomic profile of NovasoyŇ - soy isoflavone concentrate in the prostate of Nrf2 deficient and wild type mice. J. Pharm. Sci. 2008 Jan 30. [Epub ahead of print] (in press) Gopalakrishnan, A., Khor, T.O., Hao, X.P., Keum, Y.S., Yang, C.S., Reddy, B.S., and Kong, A.N.T. Murine Prostate cancer inhibition by dietary phytochemicals – Curcumin and Phenyethylisothiocyanate. Pharmaceutical Research 2008 Apr 25. [Epub ahead of print] (in press). Li, W., Yu, S.-W., Liu, T., Kim, J._H., Li, H., Blank, V., and Kong, A.-N.T. Heterodimerization with small Maf proteins enhance nuclear retention of Nrf2 via masking the NESzip motif. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (in press; 2008 Jun 9. [Epub ahead of print]) Kong, A.N.T. Theme Section on Cancer Chemoprevention. Pharm Res. 2008 Jun 25. [Epub ahead of print] No abstract available. . 2007 Nair, S., Xu, C., Shen, G., Hebbar, V., Gopalakrishnan, A., Hu, R., Jain, M.R., Liew, C.,Chan, J.Y., and Kong, A.N.T. Toxicogenomics of Endoplasmic reticum stress inducer tunicamycin in the small intestine and liver of Nrf2 Knockout and C57BL/6J Mice. Toxicol. Lett. 168:21-39, 2007. Shen, G.S., Hong, J.L., and Kong, A.N.T. Development and validation of an HPLC method for the determination of dibenzoylmethane in rat plasma and its application to the pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. Jan 10; 2007. Nair, S., Li, W. and Kong,
A.N.T. Natural dietary anti-cancer chemopreventive
compounds: redox-mediated differential signaling
mechanisms in cytoprotection of normal cells versus
cytotoxicity in tumor cells. Acta Pharmacol Sin. Apr;28(4):459-72, 2007. (Front Cover
of the Journal Issue) Yu, S. and Kong, A.N.T. Targeting at carcinogen metabolism by dietary cancer chemopreventive compounds. Current Drug Targets Review 7:416-424, 2007 [Aug. 19 Epub ahead of print]. (Invited Review). Kong, A.N.T. Molecular targets, biomarkers and animal models for anti-cancer pharmacological research: Potentials and Challenges from chemoprevention to chemotherapeutic treatment. Acta Pharmacologica Sinica Sep;28(9):1261. No abstract available. (Editorial). Kwon, J.H., Barve, A., Yu, S. Huang, M.T., and Kong, A.N.T. Cancer Chemoprevention of Phytochemicals: Potential Molecular targets, Biomarkers and Animal Models. Acta Pharmacologica Sinica Sep;28(9):1409-21, 2007. (Invited Review). .Prawan, A., Khor, T.O. and Kong, A.N.T. Application of pharmacogenomics to dietary cancer chemoprevention. (Invited review). Current Pharmacogenomics 5: 190-200, 2007. Zheng, X., Cui, X.X., Avila, G.E., Huang, M.T., Liu, Y., Patel, J., Kong, A.N.T., Paulino, R., Shih, W.J., Lin, Y., Rabson, A.B., Reddy, B.S., and Conney, A.H. Atorvastatin and celecoxib inhibit prostate PC-3 tumors in immunodeficient mice. Clinical Cancer Research 13: 5480-5487, 2007. Shen, G.S., Khor, T.O., Hu, R., Yu, S., Nair, S., Ho, C.-T., Reddy, B.S., Huang, M.-T., Newmark, H.L., and Kong, A.N.T. Chemoprevention of familial adenomatous polyposis by natural dietary compounds sulforaphane and dibenzoylmethane alone and in combination in ApcMin/+ mice. Cancer Research Oct 15;67(20):9937-9944, 2007. 2006 Khor, T.O., Keum, Y.-S., Lin, W., Kim, J.H., Hu, R., Shen,
G., Gopalkrishnan, A., Reddy, B.,
Zheng, X., Conney, A., and Kong, A.-N.T. Combined inhibitory Effects of Curcumin and Phenethyl isothiocyanate (PEITC) on the Growth of Human PC-3
Prostate Xenografts in Immunodeficient
Mice. Cancer Res. Jan 15;66(2):613-621, 2006 (Priority Report). [This manuscript has received quite a lot of media
attention]. Shen, G., Xu, C., Hu, R.,
Jain, M.R., Nair, S., Lin, W., Yang, C.S., Chan, J.Y., and Kong, A.-N.T.
Modulation of Nrf2-mediated gene expression by cancer chemopreventive
agent curcumin in C57BL/6J mice and C57BL/6J/Nrf2
(-/-) mice. Mol. Cancer Ther. 5: 39-51,
2006. Jeong, S.-S., Jun, M. and
Kong, A.-N.T. Nrf2: A potential molecular target for
cancer chemoprevention by natural compounds. Antioxidants and Redox Signalling
(Invited Review) Jan-Feb;8(1-2):99-106, 2006. Hu, R., Xu, C., Shen,
G., Jain, M.R., Khor, T.O.,
Gopalkrishnan, A., Lin, W., Reddy, B., Chan, J.Y., and Kong, A.-N.T.
Gene Expression Profiles Induced by Cancer Chemopreventive
Isothiocyanate Sulforaphane
in the Liver of C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice. Cancer Let. Nov 18;243(2):170-92.
Epub 2006 Mar 3.
Reddy, B.S., Wang, X.X.,
Steele, V., Kopelovich, L., Kong, A.-N.T.,
Khor, T.O., Zheng, X., and Rao, C.V. Prevention of colon cancer by
combination of low doses of atorvastatin, aspirin
and celecoxib in F 334 rats. Cancer Research Apr 15;66(8):4542-6. Hu, R., Khor, T.O., Shen,
G., Jeong, W.-S., Hebbar, V., Chen, C., Xu, C., Reddy, B., Chada, K. and Kong, A.-N.T. Cancer chemoprevention
of intestinal polysis in ApcMin/+
mice by sulforaphane, a natural product derived
from cruciferous vegetable. Carcinogenesis
Oct;27(10):2038-46, 2006. Epub
2006 May 4. [This manuscript has received quite a bit of media attention]. Yuan, X., Xu, C., Pan,
Z., Keum, Y.-S., Kim, J.-H., Shen, G., Yu, S., Khor, T.O., Ma, J., and Kong, A.-N.T. Butylated
Hydroxyanisole Regulates ARE-mediated Gene Expression
via Nrf2 Coupled with ERK and JNK Signaling Pathway in HepG2 cells. Mol. Carcinog.
Nov;45(11):841-50, 2006 [Epub
ahead of print May 31, 2006]. Zheng, X., Chang, R.L.,
Cui, X.-X., Avila, G.E., Hebbar, V., Gazotto, M.,
Shih, W.J., Lin, Y., Lu, S.-E., Rabson, A.B., Kong,
A.-N.T. , and Conney, A.H. Effects of
12-O-tetradecanoylphorbol-12-acetate (TPA) in combination with paclitaxel (Taxol) on prostate
cancer LNCaP cells cultured in vitro or grown as xenografts tumors in immunodeficient
mice. Clin. Cancer Res. Jun 1;12(11
Pt 1):3444-51, 2006. Lin, W., Shen, G., Yuan,
X., Jain, M.R, Yu, S., Zhang, A., Chen, J.D., and Kong, A.-N.T.
Regulation of Nrf2 transactivation domain activity
by p160 RAC3/SRC3 and other nuclear co-regulators. J. Biochem. Mol. Biol. May 31;39(3):304-10. 2006. Mandlekar, S., Hong, J.L., and Kong,
A.-N.T. Modulation of metabolic enzymes by dietary phytochemicals:
A review of mechanisms underlying beneficial versus unfavorable effects
(Invited review). Current Drug
Metabolism 7: 661-675, 2006. Xu, C., Huang, M.-T.,
Shen, G., Yuan, X., Lin, W., Khor, T.O., Conney, A.H., and Kong, A.-N.T. Inhibition of 7,12-dimethylbenz[a]anthracene-induced skin tumorigenesis
in C57BL/6 mice by sulforaphane is mediated by
Nrf2. Cancer Res. 66(16):8293-8296,
Aug 15, 2006. Xu, C., Yuan, X., Pan,
Z., Shen, G., Kim, J.-H., Yu, S., Khor, T.O., Li, W., Ma.,
J., and Kong, A.-N.T. Mechanism
of action of isothiocyanates: The induction of
ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2. Mol. Cancer Ther. Aug;5(8):1918-26,
2006. Keum, Y.-S., Chang,
P.P.-J., Nair, S., Kim, J.-H., Han, J.H., and Kong, A.-N.T. p38 MAPK Isoforms Phosphorylate Nrf2 and
Negatively Regulate the Antioxidant-Responsive Element (ARE) Contributing to
the Induction of Hemoxygenase-1 (HO-1). Cancer
Research Sep 1;66(17):8804-13, 2006. Gopalakrishnan, A., Xu, C., Nair, S.S., Chen,
C., Hebbar, V., and Kong, A.-N.T. Modulation of Activator Protein-1
(AP-1) and MAPK pathway by flavonoids in human
prostate cancer PC-3 cells. Arch Pharm
Res. Aug;29(8):633-44, 2006. Li, W., Yu, S.-W., Yuan,
X.-L., and Kong, A.-N.T. Nrf2 possesses a redox-sensitive
NES in the Neh5 transactivation domain. J. Biol. Chem. Sep 15;281(37):27251-63, 2006. [Epub
2006 Jun 21]. Khor, T.O., Hu, R., Shen,
G., Jeong, W.S., Hebbar, V., Chen, C., Xu, C., Reddy, B., Chada,
C., and Kong, A.N.T. Pharmacogenomics of Cancer Chemopreventive
Isothiocyanate Compound Sulforaphane
in the Intestinal Polyps of ApcMin/+ Mice. Biopharm. Drug Disposition. Sep 4;27(9):407-420 [Epub ahead of
print]. Hu, R., Xu, C., Shen, G.,
Jain, M.R., Khor, T.O., Gopalkrishnan, A., Lin, W., Reddy, B., Chan, J.Y.,
and Kong, A.-N.T. Identification
of Nrf2-regulated genes Induced by Chemopreventive Isothiocyanate PEITC Using Nrf2 Knock-out mice. Life Sciences Oct 12;79(20):1944-55.
Epub 2006 Jun 20. 2006. Khor, T.O. Ibrahim, S.
and Kong, A.-N.T. Toxicogenomics in drug
discovery and drug development: Potential applications and future challenges
(Invited Expert Review). Pharmaceutical
Research Aug;23(8):1659-64. 2006 [Epub ahead of print; July 21, 2006]. Hu, R., Shen, G.,
Yerramilli, U.R., Lin, W., Xu, C., Nair, S., and Kong, A.-N.T. In vivo
Pharmacokinetics, Activation of MAPK and Regulation of Gene Expression
Elicited by Cancer Chemopreventive compound BHA in
the Mice. Archives Pharm. Res. Oct;29(10):911-20, 2006. Nair, S., Xu, C., Shen,
G., Hebbar, V., Gopalakrishnan, A., Hu, R., Jain,
M.R., Lin, W., Keum, Y.S., Liew, C., Chan, J.Y., and Kong, A.N.T. Pharmacogenomics of Phenolic
Antioxidant Butylated Hydroxyanisole
(BHA) in the Small Intestine and Liver of Nrf2 Knockout and C57BL/6J Mice. Pharm. Res. Nov;23(11):2621-37,
2006. [Epub 2006 Sep 13]. Keum, Y.S., Han, Y.H.,
Liew, C., Kim, J.H., Xu, C., Yuan, X., Shakarjian, M.P., Chong, S., and Kong, A.N.T. Induction of Heme Oxygenase-1 (HO-1) and NAD[P]H: Quinone
Oxidoreductase 1 (NQO1) by a Phenolic
Antioxidant, Butylated Hydroxyanisole
(BHA) and Its Metabolite, tert-Butylhydroquinone (tBHQ) in Primary-Cultured Human and Rat Hepatocytes. Pharm. Res. Nov;23(11):2586-94,
2006 [Epub 2006 Oct 18]. Khor, T.O., Huang, M.T.,
Kwon, K.H., Chan, J.Y., Reddy, B.S. and Kong,
A.N.T. Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis. Cancer Research 66:11580-11584,
December 15 2006 (Priority Report). Nair, S., Xu, C., Shen,
G., Hebbar, V., Gopalakrishnan, A., Hu, R., Jain,
M.R., Liew, C., Chan, J.Y., and Kong,
A.N.T. Toxicogenomics of Endoplasmic reticum stress inducer tunicamycin
in the small intestine and liver of Nrf2 Knockout and C57BL/6J Mice. Toxicol. Lett.
168:21-39, 2007 [Epub Nov 10, 2006]. 2005: Jeong, W.-S., Keum, Y.-S., Chen, C., Jain, M.R., Shen, G.,
Li, W., Kim, J.-H., and Kong, A.-N.T. Differential expression and stability of
endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells. J. Biochem. Mol. Biol. 38: 167-176, March 31, 2005. Xu, C.-J., Li, C.Y.-T.,
and Kong, A.-N.T. Induction of Phase
I, II and III Drug Metabolism/Transport by Xenobiotics.
Arch. Pharmacal
Res. 28: 249-268, March 2005 (Invited Review). Hebbar, V., Shen, G., Hu,
R., Kim, B.-R., Chen, C., Korytko, P.J., Crowell,
J.A., Levine, B.F. and Kong, A.-N.T. Toxicogenomics of
resveratrol in rat liver. Life Sciences 76:
2299-2314, April 2005 (Available online January 29, 2005). Xu, C.-J., Shen, G.,
Chen, C., Genlinas, C., and Kong, A.-N.T. Suppression of NF-kB and NF-kB-regulated
Gene Expression by sulforaphane and PEITC through IkBa, IKK
pathway in human Prostate PC-3 cells. Oncogene Jun 30;24(28):4486-95,
2005 (available online March 18, 2005). Chen, C. and Kong, A.-N.T. Dietary cancer-chemopreventive
compounds: from signaling and gene expression to pharmacological effects (Invited
Review). Trends in Pharmacol. Sci. June;
26(6):318-326, 2005 (Available online 6 May 2005). Li, W., Jain, M.R., Chen,
C., Yue, X., Hebbar, V., Zhou, R. and Kong, A.-N.T. NRF2 possesses a Redox-insensitive
nuclear export signal overlapping with the leucine
zipper motif. J. Biol. Chem. Aug 5;280(31):28430-8.
2005. [Epub ahead of print May 23, 2005]. Shen, G., Xu, C., Hu, R.,
Jain, M.R., Nair, S., Lin, W., Yang, C.S., Chan, J.Y., and Kong, A.-N.T.
Comparison of (-)-epigallocatechin-3-gallate elicited liver and small
intestine gene expression profiles between C57BL/6J mice and C57BL/6J/Nrf2
(-/-) mice. Pharmaceutical Research, 22(11): 1805-20, November 2005. [Epub August 16, 2005]. Shen, G., Xu, C., Chen,
C., Hebbar, V., and Kong, A.-N.T. p53-independent G1
cell cycle arrest of human colon carcinoma cells HT-29 by sulforaphane
is associated with induction of p21CIP1 and inhibition of expression of cyclin D1. Cancer Chemother.
Pharmacol. Feb;57(3):317-27,
2006. [Epub 2005 Sep 17]. Xu, C., Shen, G., Yuan,
X., Nair, S., Kim, J.H., Gopalkrishnan, A., and Kong, A.-N.T. ERK and JNK signaling pathways are involved
in the regulation of activator protein 1 and cell death elicited by isothiocyanates in PC-3 cells. Carcinogenesis Mar;27(3):437-45, 2006. [Epub 2005
Nov 4]. Keum, Y.-S., Jeong,
W.-S., and Kong,
A.-N.T. Chemopreventive functions of isothiocyanates. Drugs News Perspectives (Invited
Review). 18: No. 7, September, 445-451, 2005. Kim, J.H., Xu, C., Shen,
G., Keum, Y.-S., Reddy, B., Conney, A., and Kong, A.-N.T. Inhibition of EGFR signaling in human
prostate cancer PC-3 cells by combination treatment with beta-Phenylethyl isothiocyanate and Curcumin. Carcinogenesis Mar;27(3):475-82,
2006. [Epub 2005 Nov 19]. Shen, G., Jeong, W.-S.,
Hu, R., and Kong, A.-N.T. Regulation of Nrf2, AP-1 and NF-kB signaling pathways by chemopreventive
agents. Antioxidants and Redox Signalling
Nov-Dec;7(11-12):1648-63. 2005 (Invited Review). 2004: Jeong, W.-S., Kim, I.-W.,
Hu, R., and Kong, A.-N.T. Modulatory properties of various natural chemopreventive agents on the activation of NF-kappaB signaling pathway. Pharmaceutical Research
21: 661-670, April 2004. Hu, R., Hebbar, V., Kim,
B.R., Chen, C., Winnik, B., Buckley, B., Soteropoulos, P., Tolias, P.,
Hart, R.P., and Kong, A.-N.T. In vivo
pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in
the rat. J. Pharmacol. Exp. Ther.
July; 310 (1): 263-71, 2004. (Feb 26, 2004 – Epub
ahead of print). Shen, G., Hebbar, V.,
Nair, S., Xu, C., Li, W., Lin, W., Keum, Y.-S., Han, J., Chen, C., and Kong, A.-N.T. Dietary chemopreventive compounds and EpRE
signaling (Invited review). Free Radical Biology and Medicine, June
15; 36: 1505-16, 2004. Chen, C., Pung, D.,
Leong, V., Hebbar, V., Shen, G., Nair, S., Li, W., and Kong, A.-N.T. Induction of detoxifying enzymes by garlic organosulfur compounds:
Role of Nrf2, chemical structure and stress signals. Free Radical
Biology and Medicine, 37: Issue 10, November 15, 1578-1590, 2004
(Available online August 13, 2004). Kong, A.-N.T. Signal transduction in cancer chemoprevention. Mutation
Research 555: Issue 1-2, November 2, 1-2, 2004 (Editorial). Keum, Y. Jeong, W.-S.,
and Kong, A.-N.T. Chemoprevention
by isothiocyanates and their underlying molecular
mechanisms. Mutation Research 555: Issue 1-2, November 2, 191-202,
2004 (Invited Review). 2003: Kim, B.-R., Hu, R., Keum, Y.-S., Hebbar, V., Shen, G. and Kong,
A.-N.T. Effects of glutathione on antioxidant response element-mediated
gene expression and apoptosis elicited by sulforaphane.
Cancer Research 63: 7520-7525, 2003. Keum, Y., Owuor, E.D., Kim, B.-R., Hu, R. and Kong, A.-N.T. Involvement
of Nrf2 and JNK in the activation of antioxidant responsive element (ARE) by phenethyl isothiocyanate
(PEITC) chemopreventive agent. Pharmaceutical
Research 20: 1351-1356, 2003. Chen, C., Shen, G.,
Hebbar, V., Hu, R., Owuor, E.D., and Kong,
A.-N.T. Epigallocatechin-3-gallate-induced stress signals in HT-29 human
colon adenocarcinoma cells. Carcinogenesis 24:1369-1378,
2003. Hu, R., Chen, C., Kim,
B.R., and Kong, A.-N.T. The roles of JNK and apoptotic signaling
pathways in PEITC-mediated pharmacodynamics
responses in human HT-29 colon cancer cells. Carcinogenesis 24:
1361-1367, 2003. Jiang, Z., Chen, C.,
Yang, B., Hebbar, V., and Kong, A.-N.T. Induction of Phase II Drug
Metabolizing Enzymes by Xenobiotics in Seven
Mammalian Cell Lines. Life Sciences 72(20): 2243-2253, 2003. 2002: Chen, Y.-R., Han, J., Kori, R., Kong,
A.-N.T. and Tan, T.-H. Phenylethyl isothiocyanate induces apoptotic signaling via
suppressing phosphatase activity against c-Jun
N-terminal kinase. J. Biol. Chem. 277:39334-39342,
2002. Misra, P., Owuor,
E.D., Li, W., Yu, S., Qi, C., Meyer, K., Zhu, Y.-J., Rao, M.S., Kong,
A.-N.T. and Reddy, J.K. Phosphorylation of
transcriptional coactivator peroxisome
proliferator-activated receptor (PPAR)-binding
protein (PBP). Stimulation of Transcriptional Regulation by Mitogen-activated Protein Kinase.
J. Biol. Chem. 277(50):48745-54, Dec 13; 2002. Rushmore, T.H. and Kong,
A.-N.T. Pharmacogenomics, Regulation and Signaling Pathways for Phase I
and II Drug Metabolizing Enzymes (Invited Review) Current Drug Metabolism
3: 481-490, 2002. Owour, E. and Kong, A.-N.T. Antioxidants
and Oxidants Regulated Signal Transduction Pathways (Invited Review). Biochemical
Pharmacology 64: 765-770, 2002. 2001: Mandlekar, S., and Kong, A.-N.T.
Mechanisms of tamoxifen-induced apoptosis. Apoptosis
6: 469-477, 2001. Yu, R., Hebbar, V., Kim,
D., Mandlekar, S., Pezzuto,
J., and Kong, A.-N.T. Resveratrol inhibits phorbol ester and UV-induced AP-1 activation by
interfering with tyrosine kinase and mitogen-activated protein kinase
pathways. Molecular Pharmacology 61: 217-224, 2001. Kong, A.-N.T., Owour,
E., Yu, R., Hebbar, V., Chen, C., Hu, R., and Mandlekar,
S. Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile
response element (ARE/EpRE). Drug Metabolism
Reviews 33: 255-271, 2001. Kong, A.-N.T., Yu, R., Owour,
E., Hebbar, V., Chen, C., Hu, R., Ee, R. and Mandlekar, S. Signal transduction events elicited by
cancer prevention compounds. (Invited review). Mutation Research 480-481:
231-241, 2001. 2000: Mandlekar, S., Hebbar, V., Christov, K., and Kong, A.-N.T. Pharmacodynamics of tamoxifen
and its 4-hydroxy and N-desmethyl metabolites:
Activation of caspases and induction of apoptosis
in rat mammary carcinoma and in human breast cancer cell lines. Cancer
Res., December 1, 60: 6601-6606, 2000. Mandlekar, S., Yu, R., Tan, T.-H., and Kong,
A.-N.T. Activation of caspase-3 and c-Jun N-terminal kinase-1 (JNK1)
signaling pathways in tamoxifen-induced apoptosis
in human breast cancer cells. Cancer Res., November 1, 60:5995-6000,
2000. Yu, R., Chen, C., Mo, Y.,
Hebbar, V., Owour, E.D., and Kong, A.-N.T.
Activation of mitogen-activated protein kinase pathways induces antioxidant response
element-mediated gene expression via Nrf2-dependent mechanim.
J. Biol. Chem., 275: December 22, 39907-39913, 2000 (in press
ˇV September 13, 2000). Yu, R., Mandlekar, S., and Kong, A.-N.T. Molecular
mechanisms of butylated hydroxylanisol-induced
toxicity: Induction of apoptosis through direct release of cytochrome c. Mol. Pharmacol.,
58: 431-437, 2000. Yu, R., Mandlekar, S., Ruben, S., Ni, J., and Kong, A.-N.T.
TRAIL-mediated apoptosis in androgen-independent prostate cancer cells. Cancer
Res., 60: 2384-2389, 2000. Yu, R., Mandlekar, S., Tan, T.-H., and Kong, A.-N.T.
Protein kinase C-independent activation of c-Jun
N-terminal kinase, p38, and apoptosis by chelerythine. J. Biol. Chem., 275:
9612-9619, March 31, 2000. Kong, A.-N.T., Yu, R., Chen, C., Mandlekar, S., and Primiano, T.
Signal transduction events elicited by natural products: Role of MAPK and caspase pathways in homeostatic response and induction of
apoptosis. Arch. Pharm. Res., 23: 1-16, 2000 (Invited Review). Yu, R., Mandlekar, S., Lei, W., Tan, T.-H., and Kong, A.-N.T.
p38 mitogen-activated protein kinase
negatively regulates antioxidant response element-mediated gene expression. J.
Biol. Chem., 275: 2322-2327, Jan 28, 2000. 1999: Yu, R., Lei, W., Mandlekar, S.,
Weber, M.J., Der, C.J., Wu, J., and Kong,
A.-N.T. Role of a mitogen-activated protein kinase pathway in the induction of Phase II detoxifying
enzymes by chemicals. J. Biol. Chem., 274: 27545-27561, 1999. Kong, A.-N.T., Mandlekar,
S., Yu, R., Lei, W., and Fasanmade, A. Pharmacodynamics and toxicodynamics
of drug action: Signaling in cell survival and cell death. Pharm. Res.,
16: 790-798, 1999 (Review). 1998 and Earlier: Yu, R., Mandlekar, S., Lei,W., Yu, R., Mandlekar, S. and Kong,
A.-N.T. Induction of apoptosis and activation of ICE/Ced-3 protease (caspase 3) and c-jun N-terminal
kinases 1 by benzo[a]pyrene. Cancer Res., 58: 2102-2106, 1998. Yu, R., Tan, T.-H, and Kong,
A.-N.T. Phenolic antioxidants, butylated hydroxyanisole (BHA)
and its metabolite tert-butylhydroquinone (BHQ)
differentially regulate mitogen-activated protein kinases. J. Biol. Chem., 272: 28962-70,
1997. Yu, R., Jiao J., Duh,
J.-L., Tan, T.-H., and Kong, A.-N.T. Activation of mitogen-activated
protein kinases by green tea polyphenols:
potential signaling pathways in the regulation of antioxidant-responsive
element-mediated phase II enzyme gene expression. Carcinogenesis, 18:
451-456, 1997. Yu, R., Jiao J., Duh,
J.-L., Tan, T.-H., and Kong, A.-N.T. Phenethyl
isothiocyanate, A natural chemopreventive
agent, activates c-jun N-terminal kinase 1 (JNK1). Cancer Res., 56:
2954-2959, 1996. Hellriegel, E.T., Matwyshyn,
G.A., Fei, P., Dragnev, K.H., Nims,
R.W., Lubet, R.A., and Kong, A.-N.T.
Regulation of phase I and phase II detoxifying enzymes sulfotransferases
and UDP-glucuronosyltransferases gene expression by
tamoxifen in rat liver. Biochem.
Pharmacol., 52:
1561-1568, 1996. Fei, P., Matwyshyn, G.A., Rushmore, T.H., and Kong, A.-N.T.
Transcription regulation of rat glutathione S-transferase
Ya subunit gene expression by chemopreventive
agents. Pharm. Res., 13: 1043-1048, (1996). Kong, A.-N.T., Fei, P., and Wong, B.K.
Differential expression of phenol family of of UDP-glucuronosyltransferases in hepatoma
cell lines. Pharm. Res., 12: 309-312, 1995. Kong, A.-N.T., Tamasko,
L., Waldman, S., Osborne, B., Deutsch, P., Goldberg, M., and Bjornsson, T.D. Losartan does
not affect the pharmacokinetics and pharmacodynamics
of warfarin. J. Clin. Pharmacol., 35:1008-1015, 1995. Kong, A.-N.T., and Fei, P. Molecular cloning of
three sulfotransferase cDNAs
from mouse liver. (2nd International Workshop on the Sulfation
of Xenobiotics and Endogenous Compounds, June 3-6,
1993, Kong, A.-N.T., Ma, M., Tao, D., and Yang, L.
Molecular cloning of two cDNAs encoding the mouse bilirubin/phenol family of UDP-glucuronosyltransferases
(ugtBr/p). Pharm. Res., 10: 461-465,
1993. Kong, A.-N.T., Yang, L., Ma, M., Tao, D., and Bjornsson, T.D. Molecular cloning of the alcohol/hydroxysteroid form (hSTa) of sulfotransferase from human liver. Biochem.
Biophys. Res. Commun.,
187: 448-454, 1992. Wange, R.L., Kong, A.-N.T. and Samelson, L.E. A Tyrosine-Phosphorylated
70 kDa Protein Binds a Photoaffinity
Analogue of ATP and Associates with Both the Zeta Chain and CD3 Components of
the Activated T Cell Antigen Receptor. J. Biol. Chem., 267:
11685-11688, 1992. Petersen, D.D., Kong,
A.-N.T., Jorge, L.F., Nebert, D.W. and Arias,
T.D. Debrisoquine polymorphism: Novel CYP2D6 gene BamHI RFLP in the Ngawbe Guaymi Indian of Kong, A.-N. and Jusko, W.J. Disposition of methylprednisolone
and its sodium succinate prodrug
in vivo and in perfused liver of rats: Nonlinear
and Sequential First-Pass Metabolism. J. Pharm. Sci., 80:
409-415, 1991. Kong, A.-N., Ludwig, E., Slaughter, R., DiStefano, P., DeMasi, J.,
Middleton, E. and Jusko, W.J. Pharmacokinetics and pharmacodynamic modeling of direct suppression effects of
methylprednisolone on serum cortisol
and blood histamine in man. Clin. Pharmacol. Ther., 46:
616-628, 1989. Kong, A.-N. and Jusko, W.J. Definitions and applications of mean
transit/residence time to a two-compartment mammillary
plasma clearance model. J. Pharm. Sci., 43: 157-165, 1988. |
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