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Novel 20-epi-vitamin D3 analog combined with 9-cis-retinoic acid markedly inhibits colony growth of prostate cancer cells

1999; Wiley; Volume: 40; Issue: 3 Linguagem: Inglês

10.1002/(sici)1097-0045(19990801)40

1097-0045

Elena Elstner, Moray J. Campbell, Reinhold Munker, Peter Shintaku, Lise Binderup, David Heber, Jonathan W. Said, H. Phillip Koeffler,

Vitamin D Research Studies

The ProstateVolume 40, Issue 3 p. 141-149 Novel 20-epi-vitamin D3 analog combined with 9-cis-retinoic acid markedly inhibits colony growth of prostate cancer cells Elena Elstner, Corresponding Author Elena Elstner [email protected] Division of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaDivision of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd., B208, Los Angeles, CA 90048Search for more papers by this authorMoray J. Campbell, Moray J. Campbell Division of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorReinhold Munker, Reinhold Munker Division of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorPeter Shintaku, Peter Shintaku Departments of Medicine and Pathology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorLise Binderup, Lise Binderup Department of Biology, Leo Pharmaceutical Products, Ballerup, DenmarkSearch for more papers by this authorDavid Heber, David Heber Center for Human Nutrition, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorJonathan Said, Jonathan Said Departments of Medicine and Pathology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorH. Phillip Koeffler, H. Phillip Koeffler Division of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this author Elena Elstner, Corresponding Author Elena Elstner [email protected] Division of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaDivision of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd., B208, Los Angeles, CA 90048Search for more papers by this authorMoray J. Campbell, Moray J. Campbell Division of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorReinhold Munker, Reinhold Munker Division of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorPeter Shintaku, Peter Shintaku Departments of Medicine and Pathology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorLise Binderup, Lise Binderup Department of Biology, Leo Pharmaceutical Products, Ballerup, DenmarkSearch for more papers by this authorDavid Heber, David Heber Center for Human Nutrition, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorJonathan Said, Jonathan Said Departments of Medicine and Pathology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this authorH. Phillip Koeffler, H. Phillip Koeffler Division of Hematology-Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CaliforniaSearch for more papers by this author First published: 29 June 1999 https://doi.org/10.1002/(SICI)1097-0045(19990801)40:3 3.0.CO;2-CCitations: 39AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract BACKGROUND 1,25 dihydroxyvitamin D3 (1,25D) and retinoids may play an important role in preventing progression of prostate cancer. METHODS We examined the ability of four novel 20-epi-vitamin D3 analogs (CB1093, KH1060, KH1266, and CB1267), either alone or in combination with 9-cis retinoic acid (RA) to inhibit colony growth of a human prostate cancer cell line, LNCaP, using soft agar as well as bone marrow stroma. Also, the effect of these analogs on the cell cycle and expression of Ki-67, p21waf−1, and p27kip1 in LNCaP cells was examined. RESULTS The analog CB1267 was the most potent, with 8 × 10−10 M of the analog inhibiting 50% colony growth (ED50) of LNCaP. 9-cis-RA also inhibited colony growth of LNCaP (ED50, 5 × 10−7 M). Combined, CB1267 and 9-cis-RA synergistically inhibited colony growth and significantly increased the number of LNCaP cells in G0/G1 phase. Cell cycle arrest was associated with increased levels of p21waf−1 and p27kip1 and decreased expression of Ki-67 protein. Pulse-exposure to this combination (5 × 10−8 M) irreversibly inhibited colony growth, both in soft agar and on normal human bone marrow stroma. CONCLUSIONS Combination of a new vitamin D3 analog (CB1267) and a retinoid (9-cis-RA) potently inhibited colony formation of LNCaP prostate cancer cells in vitro, suggesting further studies in animal models. This combination may afford an interesting therapeutic approach to low-burden prostate cancer. Prostate 40:141–149, 1999. © 1999 Wiley-Liss, Inc. REFERENCES 1Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Cancer 1992; 70: 2861– 2869. Medline 2Hsing AW, Comstock GW, Abbey H, Polk BF. Serologic precursors of cancer. Retinoids, carotenoids, and tocophenol and risk of prostate cancer. J Natl Cancer Inst 1990; 82: 941– 946. Medline 3Rechman ME, Hayes RB, Ziegler RG, Schatzkin A, Taylor PR, Fraumeni JF. Serum vitamin A and subsequent development of prostate cancer in the first National Health and Nutrition Examination Survey Epidemiological Follow-up Study. Cancer Res 1990; 50: 2311– 2315. Medline 4Taylor JA, Hirvonen A, Watson M, Pittman G, Mohler JL, Bell DA. Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res 1996; 56: 4108– 4110. Medline 5Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA. Prediction of bone density from vitamin D receptor alleles. Nature 1994; 367: 284– 287. Medline 6Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O'Malley BW. Cloning and expression of full length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci USA 1988; 85: 3294– 3298. Medline 7Giuere V, Ong ES, Segni P, Evans RM. Identification of a receptor for the morphogen retinoic acid. Nature 1987; 33: 624– 629. 8Kliewer SA, Umesone K, Mangelsdorf DJ, Evans RM. Retinoid X receptors interact with nuclear receptors in retinoic acid, thyroid hormone and vitamin D signaling. Nature 1992; 355: 446– 449. Medline 9Miller GJ, Stapleton GE, Ferrara JA, Lucia MS, Pfister S, Hedlund TE, Upadhya P. The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1a,25-dihydroxyvitamin D3. Cancer Res 1992; 52: 515– 520. Medline 10Campbell MJ, Elstner E, Holden S, Uskokovic M, Koeffler HP. 19-nor-hexafluoride analogs of vitamin D3 induce a cell cycle arrest-mediated differentiation of prostate cancer cells: LNCaP, PC-3 and DU-145. J Mol Endocrinol 1997; 19: 15– 27. Medline 11Skowronski RJ, Peehl DM, Feldman D. Vitamin D and prostate cancer: 1,25 dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. Endocrinology 1993; 132: 1952– 1960. Medline 12Chopra DP, Wilkoff LJ. Activity of retinoids against benzo(A)-pyrene-induced hyperplasia in mouse prostate organ cultures. Eur J Cancer 1979; 15: 1417– 1423. Medline 13DeVos S, Dawson MI, Holden S, Le T, Wang A, Cho SK, Chen D-L, Koeffler HP. Effects of novel, potent retinoic X receptor (RXR) specific ligands and ligands with anti-AP-1-activity on proliferation of prostate cancer cells. Prostate 1997; 32: 115– 121. Medline 14Peehl DM, Wong ST, Cramer SD, Gross C, Feldman D. Suramin, hydrocortisone, and retinoic acid modify inhibitory effects of 1,25-dihydroxyvitamin D3 on prostatic epithelial cells. Urol Oncol 1995; 1: 188– 194. 15Blutt SE, Allegretto EA, Pike JW, Weigel NL. 1,25-dihydroxyvitamin D3 and 9-cis-retinoic acid act synergistically to inhibit the growth of LNCaP prostate cells and cause accumulation of cells in G1. Endocrinology 1997; 138: 1491– 1497. Medline 16Campbell MJ, Park S, Uskokovic MR, Dawson MI, Koeffler HP. Expression of retinoic acid receptor-β sensitizes prostate cancer cells to growth inhibition mediated by combinations of retinoids and a 19-nor hexafluoride vitamin D3 analog. Endocrinology 1998; 139: 1972– 1980. Medline 17Binderup L, Latini S, Binderup E, Bretting C, Calverley M, Hansen K. 20-epi-vitamin D3 analogous: a novel class of potent regulators of cell growth and immune responses. Biochem Pharmacol 1991; 42: 1569– 1575. Medline 18Elstner E, Lee YY, Hashiya M, Pakkala S, Binderup L, Norman AW, Okamura WH, Koeffler HP. 1,25-dihydroxy-20-epi-vitamin D3: an extraordinarily potent inhibitor of leukemic cell growth in vitro. Blood 1994; 84: 1960– 1968. Medline 19Elstner E, Linker-Israeli M, Le J, Grillier I, Said J, Shintaku P, Krajewski S, Reed JC, Binderup L, Koeffler HP. Combination of potent 20-epi-vitamin D3 analog (KH 1060) and 9-cis-retinoic acid inhibits irreversibly clonal growth, decreases bcl-2 expression and induces apoptosis in HL-60 leukemic cells. Cancer Res 1996; 55: 2822– 2830. 20Elstner E, Linker-Israeli M, Lee J, Umiel T, Michl P, Said JW, Binderup L, Reed JC, Koeffler HP. Synergistic decrease of clonal proliferation, induction of differentiation, and apoptosis of acute promyelocytic leukemia cells after combined treatment with novel 20-epi vitamin D3 analogs and 9-cis retinoic acid. J Clin Invest 1997; 99: 1– 12. Medline 21Elstner E, Linker-Israeli M, Said J, Umiel T, de Vos S, Shintaku IP, Heber D, Binderup L, Uskokovic M, Koeffler HP. 20-epi-vitamin D3 analogs: a novel class of potent inhibitors of proliferation and inducers of differentiation of human breast cancer cell lines. Cancer Res 1995; 55: 2822– 2830. Medline 22De Vos S, Holden S, Heber D, Elstner E, Binderup L, Uskokovic M, Rude B, Chen DL, Cho SK, Koeffler HP. In vitro effects of potent vitamin D3 analogs on clonal proliferation of human prostate cancer cell lines. Prostate 1997; 31: 77– 82. Medline 23Munker R, Norman AW, Koeffler HP. Vitamin D compounds: effects on clonal proliferation and differentiation of human myeloid cells. J Clin Invest 1986; 87: 424– 430. 24Elstner E, Müller C, Koshizuka K, Williamson EA, Park D, Asou H, Shintaku P, Said JW, Heber D, Koeffler HP. Ligands for peroxisome proliferator-activated receptor γ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA 1998; 95: 8806– 8811. Medline 25Feldman AR, Kessler L, Myers MH, Naughton MD. The prevalence of cancer: estimates based on the Connecticut Tumor Registry. New Engl J Urol 1986; 149: 1190– 1194. 26Young CY-F, Montgomery BT, Andrews PE, Qiu S, Bilhartz DL, Tindall DJ. Hormonal regulation of prostate-specific antigen messenger RNA in human prostatic adenocarcinoma cell line LNCaP. Cancer Res 1991; 51: 3748– 3752. Medline 27Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM, Mirand EA, Murphy GP. LNCaP model of human prostatic carcinoma. Cancer Res 1983; 43: 1809– 1818. Medline 28Rubin SJ, Hailahan DL, Ashman CR, Brachman DG, Beckett MA, Virudachalam S, Yandell W, Weichselbaum RR. Two prostate carcinoma cell lines demonstrate abnormalities in tumor suppressor genes. J Surg Oncol 1991; 46: 31– 36. Medline 29Bookstein R, Rio P, Madreperla S, Hong F, Allred C, Grizzle WE, Lee W-H. Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. Proc Natl Acad Sci USA 1990; 87: 7762– 7766. Medline 30Bookstein R, MacGrogan D, Hilsenbeck SG, Sharkey F, Allred DC. p53 is mutated in a subset of advanced-stage prostate cancers. Cancer Res 1990; 53: 3369– 3373. 31Peehl DM, Wehner N, Stamey TA. Activated Ki-ras oncogene in human prostatic adenocarcinoma. Prostate 1987; 10: 281– 289. Medline 32Visakorpi T, Kallioniemi O-P, Heikkinen A, Koivula T, Isola J. Small subgroup of aggressive highly proliferative prostatic carcinomas defined by p53 accumulation. J Natl Cancer Inst 1992; 84: 883– 887. Medline 33Midland MM, Plumet Y, Okamur WH. Effect of C20 stereochemistry on the conformational profile of the side chains of vitamin D analogs. Bioorg Med Chem 1993; 3: 1799– 1804. 34Van den Bemd GJ, Pols HA, Birkenhager JC, Kleindoort WM, van Leeuwen JP. Differential effects of 1,25 dihydroxy-vitamin D3-analogs on osteoblast-like cells and on in vitro bone resorption. J Steroid Biochem Mol Biol 1995; 55: 337– 346. Medline 35Carlberg C, Mathiasen YS, Saurat Y-H, Binderup L. The 1,25-dihydroxyvitamin D3 (VD) analog MC903, EB1089 and KH1060 activate the VD receptor: homodimers show higher ligand sensitivity than heterodimers with retinoid X receptors. J Steroid Biochem Mol Biol 1995; 51: 137– 142. 36Imai Y, Pike JW, Koeffler HP. Potent vitamin D3 analogs: their abilities to enhance transactivation and to bind the vitamin D3 response element. Leuk Res 1995; 19: 147– 158. Medline 37Peleg S, Sastry M, Collins ED, Bishop YE, Norman AW. Distinct conformational changes induced by 20-epi analogs of 1a,25-dihydroxyvitamin D3 are associated with enhanced activation of the vitamin D receptor. J Biol Chem 1995; 270: 10551– 10558. Medline 38Gert-Jan CM, van den Bemd HA, Pols JC, Birkenhager JC. Conformational change and enhance stabilization of the vitamin D receptor by the 1,25-dihydroxyvitamin D3 analog KH1060. Proc Natl Acad Sci USA 1996; 93: 10685– 10690. Medline 39Hansen CM, Danielsson C, Carlberg C. The potent anti-proliferative effect of 20-epi analogues of 1,25 dihydroxyvitamin D3 in human breast-cancer MCF-7 cells is related to promoter selectivity. Int J Cancer 1996; 67: 739– 742. Medline 40Campbell MJ, Koeffler HP. Toward therapeutic intervention of cancer by vitamin D compounds. J Natl Cancer Inst 1997; 89: 182– 183. Medline 41Liu M, Lee M-H, Cohen M, Bommakanti M, Freedman LP. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 1996; 10: 142– 153. Medline 42Wang QM, Jones JB, Studzinski GP. Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells. Cancer Res 1996; 56: 264– 267. Medline 43Munker R, Kobayashi T, Elstner E, Norman AW, Uskokovic M, Zhang W, Andreeff M, Koeffler HP. A new series of vitamin D analogs is highly active for clonal inhibition, differentiation, and induction of WAF1 in myeloid leukemia. Blood 1996; 88: 2201– 2209. Medline 44Schwaller J, Koeffler HP, Nicklaus G, Loetscher P, Nagel S, Fey MF, Tobler A. Posttranscriptional stabilization underlies p53-dependent induction of p21 in differentiating human leukemic cells. J Clin Invest 1995; 95: 973– 979. Medline 45Jacob SC. Spread of prostate cancer to bone. Urology 1983; 21: 337– 344. Medline 46Dahiya R, Park HD, Cusick J, Vessella RL, Fournier G, Narayan P. Inhibition of tumorgenic potential and prostate-specific antigen expression in LNCaP human prostate cancer cell line by 13-cis-retinoic acid. Int J Cancer 1994; 59: 126– 132. Medline 47Long SH, Clarke NW, George NJR, Allen TD, Testa NG. Interaction of prostate epithelial cells from benign and malignant tumor tissue with bone-marrow stroma. Prostate 1998; 34: 203– 213. Medline 48Majewski S, Szmurlo A, Marczak M, Jablonska S, Bollag W. Inhibition of tumor cell-induced angiogenesis by retinoids, 1,25-dihydroxyvitamin D3 and their combination. Cancer Lett 1993; 75: 35– 39. Medline Citing Literature Volume40, Issue31 August 1999Pages 141-149 ReferencesRelatedInformation