Allan H. Conney Professor Rutgers University Department of Chemical Biology Ernest Mario School of Pharmacy 164 Frelinghuysen Road Piscataway. NJ 08855-0789 (732) 445-4940 FAX - 0687 aconney@rci.rutgers.edu

Cancer chemoprevention and cancer therapy by differentiating agents

Our major areas of research are (a) studies on dietary inhibitors of carcinogenesis. (b) factors influencing the metabolism and action of estradiol. and (c) anticancer effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA).

Selected Publications

Zheng X, Cui XX, Huang MT, Liu Y, Shih WJ, Lin Y, Lu YP, Wagner GC, Conney AH. (2008) Inhibitory effect of voluntary running wheel exercise on the growth of human pancreatic Panc-1 and prostate PC-3 xenograft tumors in immunodeficient mice. Oncol Rep. 19(6):1583-8.

Lu YP, Lou YR, Peng QY, Xie JG, Nghiem P, Conney AH. (2008) Effect of caffeine on the ATR/Chk1 pathway in the epidermis of UVB-irradiated mice. Cancer Res. 68(7):2523-9.

Mesia-Vela S, Sanchez RI, Roberts KG, Reuhl KR, Conney AH, Kauffman FC. (2008) Dietary clofibrate stimulates the formation and size of estradiol-induced breast tumors in female August-Copenhagen Irish (ACI) rats. Toxicology. 246(1):63-72.

Rogozin EA, Lee KW, Kang NJ, Yu H, Nomura M, Miyamoto KI, Conney AH, Bode AM, Dong Z. (2008)
Inhibitory effects of caffeine analogues on neoplastic transformation: structure-activity relationship. Carcinogenesis. Jan 14. [Epub ahead of print]

Conney AH, Kramata P, Lou YR, Lu YP. (2008) Effect of caffeine on UVB-induced carcinogenesis, apoptosis, and the elimination of UVB-induced patches of p53 mutant epidermal cells in SKH-1 mice. Photochem Photobiol. 84(2):330-8.

Zheng X, Chang RL, Cui XX, Avila G, Huang MT, Liu Y, Kong AN, Rabson AB, Conney AH. (2008)
Inhibition of NF-kappaB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells. Int J Oncol. 32(1):257-64.

Zhu BT, Gallo MA, Burger CW Jr, Meeker RJ, Cai MX, Xu S, Conney AH. (2008) Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin administration and high-fat diet on the body weight and hepatic estrogen metabolism in female C3H/HeN mice. Toxicol Appl Pharmacol. 226(2):107-18.

Zheng X, Cui XX, Avila GE, Huang MT, Liu Y, Patel J, Kong AN, Paulino R, Shih WJ, Lin Y, Rabson AB, Reddy BS, Conney AH. (2007) Atorvastatin and celecoxib inhibit prostate PC-3 tumors in immunodeficient mice. Clin Cancer Res. 13(18 Pt 1):5480-7.

Lu YP, Nolan B, Lou YR, Peng QY, Wagner GC, Conney AH. (2007) Voluntary exercise together with oral caffeine markedly stimulates UVB light-induced apoptosis and decreases tissue fat in SKH-1 mice. Proc Natl Acad Sci U S A. 104(31):12936-41.

Conney AH, Zhou S, Lee MJ, Xie JG, Yang CS, Lou YR, Lu Y. (2007) Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice. Toxicol Appl Pharmacol. 224(3):209-13.

Lu YP, Lou YR, Xie JG, Peng QY, Zhou S, Lin Y, Shih WJ, Conney AH. (2007) Caffeine and caffeine sodium benzoate have a sunscreen effect, enhance UVB-induced apoptosis, and inhibit UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis. 28(1):199-206.

Lu YP, Lou YR, Nolan B, Peng QY, Xie JG, Wagner GC, Conney AH. (2006) Stimulatory effect of voluntary exercise or fat removal (partial lipectomy) on apoptosis in the skin of UVB light-irradiated mice. Proc Natl Acad Sci U S A. 103(44):16301-6.

Xu C, Huang MT, Shen G, Yuan X, Lin W, Khor TO, Conney AH, Tony Kong AN. (2006) Inhibition of 7,12-Dimethylbenz(a)anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by Nuclear Factor E2-Related Factor 2. Cancer Res. 66(16):8293-8296.

Zheng X, Chang RL, Cui XX, Avila GE, Hebbar V, Garzotto M, Shih WJ, Lin Y, Lu SE, Rabson AB, Kong AN, Conney AH. (2006) Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate Cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice. Clin Cancer Res. 12(11 Pt 1):3444-51.

Michna L. Wagner GC. Lou YR. Xie JG. Peng QY. Lin Y. Carlson K. Shih WJ. Conney AH. Lu YP. (2006) Inhibitory effects of voluntary running wheel exercise on UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis. 27(10):2108-15.

Khor TO. Keum YS. Lin W. Kim JH. Hu R. Shen G. Xu C. Gopalakrishnan A. Reddy B. Zheng X. Conney AH. Kong AN. (2006) Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res. 66(2):613-21.

Mesia-Vela S. Sanchez RI. Reuhl KR. Conney AH. Kauffman FC. (2006) Phenobarbital treatment inhibits the formation of estradiol-dependent mammary tumors in the August-Copenhagen Irish rat. J Pharmacol Exp Ther. 317(2):590-7.

Kim JH. Xu C. Keum YS. Reddy B. Conney A. Kong AN. (2006)Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with beta-phenylethyl isothiocyanate and curcumin. Carcinogenesis. 27(3):475-82.

Schaar D. Goodell L. Aisner J. Cui XX. Han ZT. Chang R. Martin J. Grospe S. Dudek L. Riley J. Manago J. Lin Y. Rubin EH. Conney A. Strair RK. (2006) A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies.
Cancer Chemother Pharmacol. 57(6):789-95.

Hansson A. Marin YE. Suh J. Rabson AB. Chen S. Huberman E. Chang RL. Conney AH. Zheng X. (2005) Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082. an NF-kappaB inhibitor. Int J Oncol. 27(4):941-8.

Avila GE. Zheng X. Cui XX. Ryan AD. Hansson A. Suh J. Rabson AB. Chang RL. Shih WJ. Lin Y. Crowell P. Lu YP. Lou YR. Conney AH. (2005) Inhibitory effects of 12-O-tetradecanoylphorbol-13-acetate alone or in combination with all-trans retinoic acid on the growth of cultured human pancreas cancer cells and pancreas tumor xenografts in immunodeficient mice. J Pharmacol Exp Ther. 315(1):170-87.

Kramata P. Lu YP. Lou YR. Cohen JL. Olcha M. Liu S. Conney AH. (2005) Effect of administration of caffeine or green tea on the mutation profile in the p53 gene in early mutant p53-positive patches of epidermal cells induced by chronic UVB-irradiation of hairless SKH-1 mice. Carcinogenesis. 26(11):1965-74.

Kramata P. Lu YP. Lou YR. Singh RN. Kwon SM. Conney AH. (2005) Patches of mutant p53-immunoreactive epidermal cells induced by chronic UVB Irradiation harbor the same p53 mutations as squamous cell carcinomas in the skin of hairless SKH-1 mice. Cancer Res. 65(9):3577-85.

Lu YP. Lou YR. Liao J. Xie JG. Peng QY. Yang CS. Conney AH. (2005) Administration of green tea or caffeine enhances the disappearance of UVB-induced patches of mutant p53 positive epidermal cells in SKH-1 mice. Carcinogenesis. 26(8):1465-72.

Zheng X. Ryan A. Patel N. Klemons S. Hansson A. Shih WJ. Lin Y. Huberman E. Chang RL. Conney AH. (2005) Synergistic stimulatory effect of 12-O-tetradecanoylphorbol-13-acetate and capsaicin on macrophage differentiation in HL-60 and HL-525 human myeloid leukemia cells. Int J Oncol. 26(2):441-8.

Wogan GN. Hecht SS. Felton JS. Conney AH. Loeb LA. (2004) Environmental and chemical carcinogenesis. Semin Cancer Biol. 14(6):473-86.

Huang MT. Xie JG. Lin CB. Kizoulis M. Seiberg M. Shapiro S. Conney AH. (2004) Inhibitory effect of topical applications of nondenatured soymilk on the formation and growth of UVB-induced skin tumors. Oncol Res. 14(7-8):387-97.

Lu YP. Lou YR. Peng QY. Xie JG. Conney AH. Stimulatory effect of topical application of caffeine on UVB-induced apoptosis in the epidermis of p53 and Bax knockout mice. Cancer Res. (2004) 64(14):5020-7.

Mesia-Vela S. Sanchez RI. Reuhl KR. Conney AH. Kauffman FC. (2004) Dietary clofibrate inhibits induction of hepatic antioxidant enzymes by chronic estradiol in female ACI rats. Toxicology. 200(2-3):103-11.

Nagai M. Conney AH. Zhu BT. (2004)Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferase. Drug Metab Dispos. 32(5):497-504.

Conney. A.H. (2004).Tailoring cancer chemoprevention regimens to the individual. J. Cell. Biochem. 91: 277-286.

Zheng. X.. Chang. R.L.. Cui. X-X.. Avila. G.E.. Lee. S.. Lu. Y-P.. Lou. Y-R.. Shih. W.J.. Lin. Y.. Reuhl,K.. Newmark. H. Rabson. A.. and Conney. A.H. (2004). Inhibitory effect of 12-O-tetradecanoylphorbol13-acetate (TPA) alone or in combination with all-trans retinoic acid on the growth of LNCaP prostate tumors in immunodeficient mice. Cancer Res. 64: 1811-1820.

Conney. A.H. (2003). Enzyme induction and dietary chemicals as approaches to cancer chemoprevention: the Seventh DeWitt S. Goodman Lecture. Cancer Res 63: 7005-7031.

Conney. A.H. (2003). Induction of drug-metabolizing enzymes: A path to the discovery of multiple cytochromes P450. Annu. Rev. of Pharmacol. Toxicol. 43: 1-30.

Lu. Y-P.. Lou. Y-R.. Xie. J-G.. Peng. Q-Y.. Liao. J.. Yang. C.S.. Huang. M-T. and Conney. A.H. (2002). Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proc. Natl. Acad. Sci. U.S.A. 99: 12455-12460.

Lu. Y-P.. Lou. Y-R.. Li. X-H.. Xie. J-G.. Lin. Y.. Weichung. J.S. and Conney. A.H.(2002). Stimulatory effect of topical application of caffeine on UVB-induced apoptosis in mouse skin. Oncol. Res. 13: 61-70.

Zheng. X.. Ravatn. R.. Lin. Y.. Shih. W-C.. Rabson. A.. Strair. R.. Huberman. E.. Conney. A.. and Chin. K-V. (2002). Gene expression of TPA induced differentiation in HL-60 cells by DNA microarray analysis. Nucleic Acids Res. 30: 4489-4499.

Lu. Y-P.. Lou. Y-R.. Lin. Y.. Shih. W.J.. Huang. M-T.. Yang. C.S. and Conney. A.H. (2001). Inhibitory effects of orally administered green tea. black tea and caffeine on skin carcinogenesis in mice previously treated with ultraviolet B light (high risk mice): Relationship to decreased tissue fat. Cancer Res. 61: 5002-5009.

Zheng. X.. Chang. R.L.. Cui. X-X.. Kelly. K.A.. Strair. R.. Shih. W.J.. Lin. Y.. Suh. J.. Han. Z.T.. Rabson. A. and Conney. A.H. (2001) Synergistic effects of clinically achievable concentrations of 12-O tetradecanoylphorbol-13-acetate in combination with all-trans retinoic acid. 1a. 25 dihydroxyvitamin D3 and sodium butyrate on differentiation in HL-60 cells. Oncol. Res. 12: 419 427.