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Erschienen in: Tumor Biology 12/2015

01.12.2015 | Research Article

Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines

verfasst von: Canan Eroğlu, Mücahit Seçme, Gülseren Bağcı, Yavuz Dodurga

Erschienen in: Tumor Biology | Ausgabe 12/2015

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Abstract

Studies on genetic changes underlying prostate cancer and the possible signaling pathways are getting increased day by day, and new treatment methods are being searched for. The aim of the present study is to investigate the effects of ferulic acid (FA), a phenolic compound, on cell cycle, apoptosis, invasion, and colony formation in the PC-3 and LNCaP prostate cancer cells. The effect of FA on cell viability was determined via a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method. Total RNA was isolated with Tri Reagent. Expression of 84 genes for both cell cycle and apoptosis separately was evaluated by reverse transcriptase PCR (RT-PCR). Protein expressions were evaluated by Western blot analysis. Furthermore, apoptotic effects of FA were observed with terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assay. Effects of FA on cell invasion and colony formation were determined using Matrigel chamber and colony assay, respectively. The half maximal inhibitory concentration (IC50) dose of FA was found to be 300 μM in PC-3 cells and 500 μM in LNCaP cells. According to RT-PCR results, it was observed that FA inhibited cell proliferation by increasing the gene expressions of ATR, ATM, CDKN1A, CDKN1B, E2F4, RB1, and TP53 and decreasing the gene expressions of CCND1, CCND2, CCND3, CDK2, CDK4, and CDK6 in PC-3 cells. On the other hand, it was seen that FA suppressed cell proliferation by increasing in the gene expressions of CASP1, CASP2, CASP8, CYCS, FAS, FASLG, and TRADD and decreasing in the gene expressions of BCL2 and XIAP in LNCaP cells. In this study, protein expression of CDK4 and BCL2 genes significantly decreased in these cells. It could induce apoptosis in PC-3 and LNCaP cells. Also, it was observed that FA suppressed the invasion in PC-3 and LNCaP cells. Moreover, it suppressed the colony formation. In conclusion, it has been observed that FA may lead to cell cycle arrest in PC-3 cells while it may cause apoptosis in LNCaP cells.
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Literatur
3.
Zurück zum Zitat Chin JL, Reiter RE. Molecular markers and prostate cancer prognosis. Clin Prostate Cancer. 2004;3(3):157–64.CrossRefPubMed Chin JL, Reiter RE. Molecular markers and prostate cancer prognosis. Clin Prostate Cancer. 2004;3(3):157–64.CrossRefPubMed
4.
Zurück zum Zitat Velcheti V, Karnik S, Bardot SF, Prakash O. Pathogenesis of prostate cancer: lessons from basic research. Ochsner J. 2008;8(4):213–8.PubMedPubMedCentral Velcheti V, Karnik S, Bardot SF, Prakash O. Pathogenesis of prostate cancer: lessons from basic research. Ochsner J. 2008;8(4):213–8.PubMedPubMedCentral
5.
Zurück zum Zitat Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320–8.CrossRefPubMed Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320–8.CrossRefPubMed
6.
Zurück zum Zitat Fresco P, Borges F, Diniz C, Marques MP. New insights on the anticancer properties of dietary polyphenols. Med Res Rev. 2009;26(6):747–66.CrossRef Fresco P, Borges F, Diniz C, Marques MP. New insights on the anticancer properties of dietary polyphenols. Med Res Rev. 2009;26(6):747–66.CrossRef
7.
Zurück zum Zitat Fresco P, Borges F, Marques MP, Diniz C. The anticancer properties of dietary polyphenols and its relation with apoptosis. Curr Pharm Des. 2010;16(1):114–34.CrossRefPubMed Fresco P, Borges F, Marques MP, Diniz C. The anticancer properties of dietary polyphenols and its relation with apoptosis. Curr Pharm Des. 2010;16(1):114–34.CrossRefPubMed
8.
Zurück zum Zitat Huang WY, Cai YZ, Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutr Cancer. 2010;62(1):1–20.CrossRefPubMed Huang WY, Cai YZ, Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutr Cancer. 2010;62(1):1–20.CrossRefPubMed
9.
Zurück zum Zitat D’Archivio M, Filesi C, Di Benedetto R, Gargiulo R, Giovannini C, Masella R. Polyphenols, dietary sources and bioavailability. Ann Ist Super Sanita. 2007;43(4):348–61.PubMed D’Archivio M, Filesi C, Di Benedetto R, Gargiulo R, Giovannini C, Masella R. Polyphenols, dietary sources and bioavailability. Ann Ist Super Sanita. 2007;43(4):348–61.PubMed
10.
Zurück zum Zitat Clifford MN. Chlorogenic acids and other cinnamates—nature, occurrence and dietary burden. J Sci Food Agric. 1999;79:362–72.CrossRef Clifford MN. Chlorogenic acids and other cinnamates—nature, occurrence and dietary burden. J Sci Food Agric. 1999;79:362–72.CrossRef
11.
Zurück zum Zitat Carbone C, Campisi A, Musumeci T, Raciti G, Bonfanti R, Puglisi G. FA-loaded lipid drug delivery systems: preparation, characterization and biological studies. Eur J Pharm Sci. 2014;52:12–20.CrossRefPubMed Carbone C, Campisi A, Musumeci T, Raciti G, Bonfanti R, Puglisi G. FA-loaded lipid drug delivery systems: preparation, characterization and biological studies. Eur J Pharm Sci. 2014;52:12–20.CrossRefPubMed
12.
Zurück zum Zitat Janicke B, Hegardt C, Krogh M, Onning G, Akesson B, Cirenajwis HM, et al. The antiproliferative effect of dietary fiber phenolic compounds ferulic acid and p-coumaric acid on the cell cycle of Caco-2 cells. Nutr Cancer. 2011;63(4):611–22.CrossRefPubMed Janicke B, Hegardt C, Krogh M, Onning G, Akesson B, Cirenajwis HM, et al. The antiproliferative effect of dietary fiber phenolic compounds ferulic acid and p-coumaric acid on the cell cycle of Caco-2 cells. Nutr Cancer. 2011;63(4):611–22.CrossRefPubMed
13.
Zurück zum Zitat Knudsen KE, Arden KC, Cavenee WK. Multiple G1 regulatory elements control the androgen-dependent proliferation of prostatic carcinoma cells. J Biol Chem. 1998;273(32):20213–22.CrossRefPubMed Knudsen KE, Arden KC, Cavenee WK. Multiple G1 regulatory elements control the androgen-dependent proliferation of prostatic carcinoma cells. J Biol Chem. 1998;273(32):20213–22.CrossRefPubMed
15.
Zurück zum Zitat Xu Y, Chen SY, Ross KN, Balk SP. Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and posttranscriptional increases in cyclin D proteins. Cancer Res. 2006;66(15):7783–92.CrossRefPubMed Xu Y, Chen SY, Ross KN, Balk SP. Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and posttranscriptional increases in cyclin D proteins. Cancer Res. 2006;66(15):7783–92.CrossRefPubMed
16.
Zurück zum Zitat Brooks JD, Bova GS, Isaacs WB. Allelic loss of the retinoblastoma gene in primary human prostatic adenocarcinomas. Prostate. 1995;26(1):35–9.CrossRefPubMed Brooks JD, Bova GS, Isaacs WB. Allelic loss of the retinoblastoma gene in primary human prostatic adenocarcinomas. Prostate. 1995;26(1):35–9.CrossRefPubMed
17.
Zurück zum Zitat Ittmann MM, Wieczorek R. Alterations of the retinoblastoma gene in clinically localized, stage B prostate adenocarcinomas. Hum Pathol. 1996;27(1):28–34.CrossRefPubMed Ittmann MM, Wieczorek R. Alterations of the retinoblastoma gene in clinically localized, stage B prostate adenocarcinomas. Hum Pathol. 1996;27(1):28–34.CrossRefPubMed
18.
Zurück zum Zitat Tricoli JV, Gumerlock PH, Yao JL, Chi SG, D’Souza SA, Nestok BR, et al. Alterations of the retinoblastoma gene in human prostate adenocarcinoma. Genes Chromosomes Cancer. 1996;15(2):108–14.CrossRefPubMed Tricoli JV, Gumerlock PH, Yao JL, Chi SG, D’Souza SA, Nestok BR, et al. Alterations of the retinoblastoma gene in human prostate adenocarcinoma. Genes Chromosomes Cancer. 1996;15(2):108–14.CrossRefPubMed
19.
Zurück zum Zitat Jarrard DF, Modder J, Fadden P, Fu V, Sebree L, Heisey D, et al. Alterations in the p16/pRb cell cycle checkpoint occur commonly in primary and metastatic human prostate cancer. Cancer Lett. 2002;185(2):191–9.CrossRefPubMed Jarrard DF, Modder J, Fadden P, Fu V, Sebree L, Heisey D, et al. Alterations in the p16/pRb cell cycle checkpoint occur commonly in primary and metastatic human prostate cancer. Cancer Lett. 2002;185(2):191–9.CrossRefPubMed
20.
Zurück zum Zitat Peng CC, Chyau CC, Wang HE, Chang CH, Chen KC, Chou KY, et al. Cytotoxicity of Ferulic acid on T24 cell line differentiated by different microenvironments. BioMed Res Int. 2013. doi:10.1155/2013/579859. Peng CC, Chyau CC, Wang HE, Chang CH, Chen KC, Chou KY, et al. Cytotoxicity of Ferulic acid on T24 cell line differentiated by different microenvironments. BioMed Res Int. 2013. doi:10.​1155/​2013/​579859.
21.
Zurück zum Zitat Hemaiswarya S, Doble M. Combination of phenylpropanoids with 5-fluorouracil as anti-cancer agents against human cervical cancer (HeLa) cell line. Phytomedicine. 2013;20(2):151–8.CrossRefPubMed Hemaiswarya S, Doble M. Combination of phenylpropanoids with 5-fluorouracil as anti-cancer agents against human cervical cancer (HeLa) cell line. Phytomedicine. 2013;20(2):151–8.CrossRefPubMed
22.
Zurück zum Zitat Cho SD, Li G, Hu H, Jiang C, Kang KS, Lee YS, et al. Involvement of c-Jun N-terminal kinase in G2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells. Nutr Cancer. 2005;52(2):213–24.CrossRefPubMed Cho SD, Li G, Hu H, Jiang C, Kang KS, Lee YS, et al. Involvement of c-Jun N-terminal kinase in G2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells. Nutr Cancer. 2005;52(2):213–24.CrossRefPubMed
24.
Zurück zum Zitat Hou Y, Yang J, Zhao G, Yuan Y. Ferulic acid inhibits endothelial cell proliferation through NO downregulating ERK1/2 pathway. J Cell Biochem. 2004;93(6):1203–9.CrossRefPubMed Hou Y, Yang J, Zhao G, Yuan Y. Ferulic acid inhibits endothelial cell proliferation through NO downregulating ERK1/2 pathway. J Cell Biochem. 2004;93(6):1203–9.CrossRefPubMed
25.
Zurück zum Zitat Dong Q, Meng P, Wang T, Qin W, Wang F, Yuan J, et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 2010;5(4):e10147.CrossRefPubMedPubMedCentral Dong Q, Meng P, Wang T, Qin W, Wang F, Yuan J, et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 2010;5(4):e10147.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Susaki E, Nakayama K, Nakayama KI. Cyclin D2 translocates p27 out of the nucleus and promotes its degradation at the G0-G1 transition. Mol Cell Biol. 2007;27(13):4626–40.CrossRefPubMedPubMedCentral Susaki E, Nakayama K, Nakayama KI. Cyclin D2 translocates p27 out of the nucleus and promotes its degradation at the G0-G1 transition. Mol Cell Biol. 2007;27(13):4626–40.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Nikoleishvili D, Pertia A, Trsintsadze O, Gogokhia N, Managadze L, Chkhotua A. Expression of p27(Kip1), cyclin D3 and Ki67 in BPH, prostate cancer and hormone-treated prostate cancer cells. Int Urol Nephrol. 2008;40(4):953–9.CrossRefPubMed Nikoleishvili D, Pertia A, Trsintsadze O, Gogokhia N, Managadze L, Chkhotua A. Expression of p27(Kip1), cyclin D3 and Ki67 in BPH, prostate cancer and hormone-treated prostate cancer cells. Int Urol Nephrol. 2008;40(4):953–9.CrossRefPubMed
28.
Zurück zum Zitat D’Angiolella V, Donato V, Vijayakumar S, Saraf A, Florens L, Washburn MP, et al. SCF(cyclin F) controls centrosome homeostasis and mitotic fidelity via CP110 degradation. Nature. 2010;466(7302):138–42.CrossRefPubMedPubMedCentral D’Angiolella V, Donato V, Vijayakumar S, Saraf A, Florens L, Washburn MP, et al. SCF(cyclin F) controls centrosome homeostasis and mitotic fidelity via CP110 degradation. Nature. 2010;466(7302):138–42.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Zieske JD. Expression of cyclin-dependent kinase inhibitors during corneal wound repair. Prog Retin Eye Res. 2000;19(3):257–70.CrossRefPubMed Zieske JD. Expression of cyclin-dependent kinase inhibitors during corneal wound repair. Prog Retin Eye Res. 2000;19(3):257–70.CrossRefPubMed
30.
Zurück zum Zitat Sirma H, Broemel M, Stumm L, Tsourlakis T, Steurer S, Tennstedt P, et al. Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion-negative prostate cancer, but is unrelated to patient prognosis. Oncol Lett. 2013;6(5):1245–52.PubMedPubMedCentral Sirma H, Broemel M, Stumm L, Tsourlakis T, Steurer S, Tennstedt P, et al. Loss of CDKN1B/p27Kip1 expression is associated with ERG fusion-negative prostate cancer, but is unrelated to patient prognosis. Oncol Lett. 2013;6(5):1245–52.PubMedPubMedCentral
31.
Zurück zum Zitat Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR. The E2F transcription factor is a cellular target for the Rb protein. Cell. 1991;65(6):1053–62.CrossRefPubMed Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR. The E2F transcription factor is a cellular target for the Rb protein. Cell. 1991;65(6):1053–62.CrossRefPubMed
32.
Zurück zum Zitat Plesca D, Crosby ME, Gupta D, Almasan A. E2F4 function in G2: maintaining G2-arrest to prevent mitotic entry with damaged DNA. Cell Cycle. 2007;6(10):1147–52.CrossRefPubMedPubMedCentral Plesca D, Crosby ME, Gupta D, Almasan A. E2F4 function in G2: maintaining G2-arrest to prevent mitotic entry with damaged DNA. Cell Cycle. 2007;6(10):1147–52.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Chinnadurai G, Vijayalingam S, Rashmi R. BIK, the founding member of the BH3-only family proteins: mechanisms of cell death and role in cancer and pathogenic processes. Oncogene. 2008;27(1):20–9.CrossRef Chinnadurai G, Vijayalingam S, Rashmi R. BIK, the founding member of the BH3-only family proteins: mechanisms of cell death and role in cancer and pathogenic processes. Oncogene. 2008;27(1):20–9.CrossRef
35.
Zurück zum Zitat Bandagula VR, Prasad NR. 2-Deoxy-glucose and ferulic acid modulates radiation response signaling in non-small cell lung cancer cells. Tumour Biol. 2013;34(1):251–9.CrossRef Bandagula VR, Prasad NR. 2-Deoxy-glucose and ferulic acid modulates radiation response signaling in non-small cell lung cancer cells. Tumour Biol. 2013;34(1):251–9.CrossRef
36.
Zurück zum Zitat Guo Y, Kyprianou N. Restoration of transforming growth factor beta signaling pathway in human prostate cancer cells suppresses tumorigenicity via induction of caspase-1-mediated apoptosis. Cancer Res. 1999;59(6):1366–71.PubMed Guo Y, Kyprianou N. Restoration of transforming growth factor beta signaling pathway in human prostate cancer cells suppresses tumorigenicity via induction of caspase-1-mediated apoptosis. Cancer Res. 1999;59(6):1366–71.PubMed
37.
Zurück zum Zitat Winter RN, Kramer A, Borkowski A, Kyprianou N. Loss of caspase-1 and caspase-3 protein expression in human prostate cancer. Cancer Res. 2001;61(3):1227–32.PubMed Winter RN, Kramer A, Borkowski A, Kyprianou N. Loss of caspase-1 and caspase-3 protein expression in human prostate cancer. Cancer Res. 2001;61(3):1227–32.PubMed
38.
Zurück zum Zitat VanOosten RL, Earel Jr JK, Griffith TS. Histone deacetylase inhibitors enhance Ad5-TRAIL killing of TRAIL-resistant prostate tumor cells through increased caspase-2 activity. Apoptosis. 2007;12(3):561–71.CrossRefPubMed VanOosten RL, Earel Jr JK, Griffith TS. Histone deacetylase inhibitors enhance Ad5-TRAIL killing of TRAIL-resistant prostate tumor cells through increased caspase-2 activity. Apoptosis. 2007;12(3):561–71.CrossRefPubMed
39.
Zurück zum Zitat Kampa M, Alexaki VI, Notas G, Nifli AP, Nistikaki A, Hatzoglou A, et al. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Res. 2004;6(2):63–74.CrossRef Kampa M, Alexaki VI, Notas G, Nifli AP, Nistikaki A, Hatzoglou A, et al. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Res. 2004;6(2):63–74.CrossRef
40.
Zurück zum Zitat Krajewska M, Krajewski S, Banares S, Huang X, Turner B, Bubendorf L, et al. Elevated expression of inhibitor of apoptosis proteins in prostate cancer. Clin Cancer Res. 2003;9(13):4914–25.PubMed Krajewska M, Krajewski S, Banares S, Huang X, Turner B, Bubendorf L, et al. Elevated expression of inhibitor of apoptosis proteins in prostate cancer. Clin Cancer Res. 2003;9(13):4914–25.PubMed
41.
Zurück zum Zitat Ramp U, Krieg T, Caliskan E, Mahotka C, Ebert T, Willers R, et al. XIAP expression is an independent prognostic marker in clear-cell renal carcinomas. Hum Pathol. 2004;35(8):1022–8.CrossRefPubMed Ramp U, Krieg T, Caliskan E, Mahotka C, Ebert T, Willers R, et al. XIAP expression is an independent prognostic marker in clear-cell renal carcinomas. Hum Pathol. 2004;35(8):1022–8.CrossRefPubMed
42.
Zurück zum Zitat Karthikeyan S, Kanimozhi G, Prasad NR, Mahalakshmi R. Radiosensitizing effect of ferulic acid on human cervical carcinoma cells in vitro. Toxicol In Vitro. 2011;25(7):1366–75.CrossRefPubMed Karthikeyan S, Kanimozhi G, Prasad NR, Mahalakshmi R. Radiosensitizing effect of ferulic acid on human cervical carcinoma cells in vitro. Toxicol In Vitro. 2011;25(7):1366–75.CrossRefPubMed
43.
Zurück zum Zitat Tsai CM, Yen GC, Sun FM, Yang SF, Weng CJ. Assessment of the anti-invasion potential and mechanism of select cinnamic acid derivatives on human lung adenocarcinoma cells. Mol Pharm. 2013;10(5):1890–900.CrossRefPubMed Tsai CM, Yen GC, Sun FM, Yang SF, Weng CJ. Assessment of the anti-invasion potential and mechanism of select cinnamic acid derivatives on human lung adenocarcinoma cells. Mol Pharm. 2013;10(5):1890–900.CrossRefPubMed
44.
Zurück zum Zitat Fang HY, Wang HM, Chang KF, Hu HT, Hwang LJ, Fu TF, et al. Feruloyl-L-arabinose attenuates migration, invasion and production of reactive oxygen species in H1299 lung cancer cells. Food ChemToxicol. 2013;58:459–66. doi:10.1016/j.fct.2013.05.019.CrossRef Fang HY, Wang HM, Chang KF, Hu HT, Hwang LJ, Fu TF, et al. Feruloyl-L-arabinose attenuates migration, invasion and production of reactive oxygen species in H1299 lung cancer cells. Food ChemToxicol. 2013;58:459–66. doi:10.​1016/​j.​fct.​2013.​05.​019.CrossRef
Metadaten
Titel
Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines
verfasst von
Canan Eroğlu
Mücahit Seçme
Gülseren Bağcı
Yavuz Dodurga
Publikationsdatum
01.12.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 12/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3689-3

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