Jaboticaba Peel Extract Exerts Chemopreventive Effects in Transgenic
Mouse Model of Prostate Cancer

Ellen      Nogueira-Lima; Celina      de Almeida Lamas; Andressa   Mara   Baseggio; Fernanda   Cristina   da Veiga; Lucia   Elvira   Álvares; Mario   Roberto Maróstica   Júnior; Valeria   Helena Alves   Cagnon

doi:10.2174/0122103155281770240104091620

Abstract

Introduction: Angiogenesis, oxidative stress, and epigenetic alterations involved in prostate cancer (PCa) are associated with different risk factors, such as a high-fat diet (HFD), overweight, and obesity. Jaboticaba peel extract (PJE) has shown antiproliferative, antiangiogenic, and antioxidant activities in the prostate of senile mice.

Method: This study aimed to evaluate the effect of PJE on the dorsolateral prostate microenvironment in male transgenic mice for the prostate adenocarcinoma model, considering different pathological alterations, changed or unchanged by HFD, focusing on histopathology, and molecules related to extracellular matrix (ECM), oxidative stress, angiogenesis, and Dact-1. Western blotting and immunohistochemistry were performed on Dact-1-associated tumor suppressor genes in transgenic mice. Mice were fed HFD and received patented jaboticaba peel extract (PJE) treatment. The plasma levels of systemic oxidative stress were evaluated.

Results: Our results showed that PJE protected the dorsolateral prostate against proliferation and increased MMP9, TGFβ, and VEGF levels. PJE reduced oxidative stress and lipid peroxidation by modulating catalase, SOD 2, and 4HNE. PJE exhibited an epigenetic action, evidenced by increased Dact-1 gene expression in PCa.

Conclusion: PJE could be a natural protector of PCa and prostate lesions associated with HFD intake.

Keywords: TRAMP mice, prostate cancer, jaboticaba, extracellular matrix, angiogenesis, Dact-1.

Graphical Abstract

[1]
Sung, H.; Ferlay, J. Siegel, RL Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.,  2021, 71(3), 209-249.

[2]
Rawla, P. Epidemiology of prostate cancer. World J. Oncol.,  2019, 10(2), 63-89.
 [http://dx.doi.org/10.14740/wjon1191] [PMID: 31068988]

[3]
Oczkowski, M.; Dziendzikowska, K.; Pasternak-Winiarska, A.; Włodarek, D.; Gromadzka-Ostrowska, J. Dietary factors and prostate cancer development, progression, and reduction. Nutrients,  2021, 13(2), 496.
 [http://dx.doi.org/10.3390/nu13020496] [PMID: 33546190]

[4]
Bostwick, D.G.; Burke, H.B.; Djakiew, D.; Euling, S.; Ho, S.; Landolph, J.; Morrison, H.; Sonawane, B.; Shifflett, T.; Waters, D.J.; Timms, B. Human prostate cancer risk factors. Cancer,  2004, 101(S10)(Suppl.), 2371-2490.
 [http://dx.doi.org/10.1002/cncr.20408] [PMID: 15495199]

[5]
Finstad, W.; Galiauskas, R.; Cook, J.; Murphy, K.; O’Connor, D.; O Sullivan, E.; Markey, G.; Murphy, C.G. Prevalence of overweight and prediabetes in men receiving systemic therapies for metastatic prostate cancer. J. Clin. Oncol.,  2018, 36(6_suppl)(Suppl.), 289.
 [http://dx.doi.org/10.1200/JCO.2018.36.6_suppl.289]

[6]
Henning, S.M.; Wang, P.; Said, J.; Magyar, C.; Castor, B.; Doan, N.; Tosity, C.; Moro, A.; Gao, K.; Li, L.; Heber, D. Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis. J. Nutr. Biochem.,  2012, 23(11), 1537-1542.
 [http://dx.doi.org/10.1016/j.jnutbio.2011.10.007] [PMID: 22405694]

[7]
Davalli, P.; Rizzi, F.; Caporali, A.; Pellacani, D.; Davoli, S.; Bettuzzi, S.; Brausi, M.; D’Arca, D. Anticancer activity of green tea polyphenols in prostate gland. Oxid. Med. Cell. Longev.,  2012, 2012, 1-18.
 [http://dx.doi.org/10.1155/2012/984219] [PMID: 22666523]

[8]
Figueiroa, M.S.; César Vieira, J.S.B.; Leite, D.S.; Filho, R.C.O.A.; Ferreira, F.; Gouveia, P.S.; Udrisar, D.P.; Wanderley, M.I. Green tea polyphenols inhibit testosterone production in rat Leydig cells. Asian J. Androl.,  2009, 11(3), 362-370.
 [http://dx.doi.org/10.1038/aja.2009.2] [PMID: 19330017]

[9]
Tam, N.N.C.; Nyska, A.; Maronpot, R.R.; Kissling, G.; Lomnitski, L.; Suttie, A.; Bakshi, S.; Bergman, M.; Grossman, S.; Ho, S.M. Differential attenuation of oxidative/nitrosative injuries in early prostatic neoplastic lesions in TRAMP mice by dietary antioxidants. Prostate,  2006, 66(1), 57-69.
 [http://dx.doi.org/10.1002/pros.20313] [PMID: 16114064]

[10]
Narita, S.; Nara, T.; Sato, H.; Koizumi, A.; Huang, M.; Inoue, T.; Habuchi, T. Research evidence on high-fat diet-induced prostate cancer development and progression. J. Clin. Med.,  2019, 8(5), 597.
 [http://dx.doi.org/10.3390/jcm8050597] [PMID: 31052319]

[11]
Fujita, K.; Hayashi, T.; Matsushita, M.; Uemura, M.; Nonomura, N. Obesity, inflammation, and prostate cancer. J. Clin. Med.,  2019, 8(2), 201.
 [http://dx.doi.org/10.3390/jcm8020201] [PMID: 30736371]

[12]
Barron, D.A.; Rowley, D.R. The reactive stroma microenvironment and prostate cancer progression. Endocr. Relat. Cancer,  2012, 19(6), R187-R204.
 [http://dx.doi.org/10.1530/ERC-12-0085] [PMID: 22930558]

[13]
Tuxhorn, J.A.; McAlhany, S.J.; Dang, T.D.; Ayala, G.E.; Rowley, D.R. Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model. Cancer Res.,  2002, 62(11), 3298-3307.
 [PMID: 12036948]

[14]
Tuxhorn, J.A.; Ayala, G.E.; Smith, M.J.; Smith, V.C.; Dang, T.D.; Rowley, D.R. Reactive stroma in human prostate cancer: Induction of myofibroblast phenotype and extracellular matrix remodeling. Clin. Cancer Res.,  2002, 8(9), 2912-2923.
 [PMID: 12231536]

[15]
Pego, E.R.; Fernández, I.; Núñez, M.J. Molecular basis of the effect of MMP-9 on the prostate bone metastasis: A review. Urol. Oncol.,  2018, 36(6), 272-282.
 [http://dx.doi.org/10.1016/j.urolonc.2018.03.009] [PMID: 29650324]

[16]
Bonkhoff, H. Analytical molecular pathology of epithelial-stromal interactions in the normal and neoplastic prostate. Anal. Quant. Cytol. Histol.,  1998, 20(5), 437-442.
 [PMID: 9801762]

[17]
Baspinar, S.; Bircan, S.; Ciris, M.; Karahan, N.; Bozkurt, K.K. Expression of NGF, GDNF and MMP-9 in prostate carcinoma. Pathol. Res. Pract.,  2017, 213(5), 483-489.
 [http://dx.doi.org/10.1016/j.prp.2017.02.007] [PMID: 28237042]

[18]
Morgia, G.; Falsaperla, M.; Malaponte, G.; Madonia, M.; Indelicato, M.; Travali, S.; Mazzarino, M.C. Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer. Urol. Res.,  2005, 33(1), 44-50.
 [http://dx.doi.org/10.1007/s00240-004-0440-8] [PMID: 15517230]

[19]
Zhong, W.; Han, Z.; He, H.; Bi, X.; Dai, Q.; Zhu, G.; Ye, Y.; Liang, Y.; Qin, W.; Zhang, Z.; Zeng, G.; Chen, Z. CD147, MMP-1, MMP-2 and MMP-9 protein expression as significant prognostic factors in human prostate cancer. Oncology,  2008, 75(3-4), 230-236.
 [http://dx.doi.org/10.1159/000163852] [PMID: 18852494]

[20]
Sampson, N.; Brunner, E.; Weber, A.; Puhr, M.; Schäfer, G.; Szyndralewiez, C.; Klocker, H. Inhibition of Nox4‐dependent ROS signaling attenuates prostate fibroblast activation and abrogates stromal‐mediated protumorigenic interactions. Int. J. Cancer,  2018, 143(2), 383-395.
 [http://dx.doi.org/10.1002/ijc.31316] [PMID: 29441570]

[21]
Papageorgis, P. TGF β signaling in tumor initiation, epithelial-to-mesenchymal transition, and metastasis. J. Oncol.,  2015, 2015, 1-15.
 [http://dx.doi.org/10.1155/2015/587193] [PMID: 25883652]

[22]
Cao, Z.; Kyprianou, N. Mechanisms navigating the TGF-β pathway in prostate cancer. Asian J. Urol.,  2015, 2(1), 11-18.
 [http://dx.doi.org/10.1016/j.ajur.2015.04.011] [PMID: 29051866]

[23]
Russo, G.; Mischi, M.; Scheepens, W.; De la Rosette, J.J.; Wijkstra, H. Angiogenesis in prostate cancer: Onset, progression and imaging. BJU Int.,  2012, 110(11c), E794-E808.
 [http://dx.doi.org/10.1111/j.1464-410X.2012.11444.x] [PMID: 22958524]

[24]
Cheyette, B.N.R.; Waxman, J.S.; Miller, J.R.; Takemaru, K.I.; Sheldahl, L.C.; Khlebtsova, N.; Fox, E.P.; Earnest, T.; Moon, R.T. Dapper, a dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation. Dev. Cell,  2002, 2(4), 449-461.
 [http://dx.doi.org/10.1016/S1534-5807(02)00140-5] [PMID: 11970895]

[25]
Ma, B.; Liu, B.; Cao, W.; Gao, C.; Qi, Z.; Ning, Y.; Chen, Y.G. The Wnt signaling antagonist dapper1 accelerates dishevelled2 degradation via promoting its ubiquitination and aggregate-induced autophagy. J. Biol. Chem.,  2015, 290(19), 12346-12354.
 [http://dx.doi.org/10.1074/jbc.M115.654590] [PMID: 25825496]

[26]
Yuan, G.; Wang, C.; Ma, C.; Chen, N.; Tian, Q.; Zhang, T.; Fu, W. Oncogenic function of DACT1 in colon cancer through the regulation of β-catenin. PLoS One,  2012, 7(3), e34004.
 [http://dx.doi.org/10.1371/journal.pone.0034004] [PMID: 22470507]

[27]
Guo, Y.; Shan, B.E.; Guo, W.; Dong, Z.M.; Zhou, Z.; Shen, S.P.; Guo, X.; Liang, J.; Kuang, G. Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma. J. Biomed. Sci.,  2017, 24(1), 6.
 [http://dx.doi.org/10.1186/s12929-016-0308-6] [PMID: 28077137]

[28]
Yin, X.; Xiang, T.; Li, L.; Su, X.; Shu, X.; Luo, X.; Huang, J.; Yuan, Y.; Peng, W.; Oberst, M.; Kelly, K.; Ren, G.; Tao, Q. DACT1, an antagonist to Wnt/β-catenin signaling, suppresses tumor cell growth and is frequently silenced in breast cancer. Breast Cancer Res.,  2013, 15(2), R23.
 [http://dx.doi.org/10.1186/bcr3399] [PMID: 23497530]

[29]
Li, R.; Liu, B.; Li, X.; Hou, L.; Mu, X.; Wang, H.; Linghu, H. DACT1 overexpression in type I ovarian cancer inhibits malignant expansion and cis-platinum resistance by modulating canonical Wnt signalling and autophagy. Sci. Rep.,  2017, 7(1), 9285.
 [http://dx.doi.org/10.1038/s41598-017-08249-7] [PMID: 28839145]

[30]
Esposito, M.; Fang, C. Cook, KC TGF-β-induced DACT1 biomolecular condensates repress Wnt signalling to promote bone metastasis. Nat. Cell Biol.,  2021, 23(3), 257-267.
 [http://dx.doi.org/10.1038/s41556-021-00641-w]

[31]
Lagathu, C.; Christodoulides, C.; Virtue, S.; Cawthorn, W.P.; Franzin, C.; Kimber, W.A.; Nora, E.D.; Campbell, M.; Medina-Gomez, G.; Cheyette, B.N.R.; Vidal-Puig, A.J.; Sethi, J.K. Dact1, a nutritionally regulated preadipocyte gene, controls adipogenesis by coordinating the Wnt/beta-catenin signaling network. Diabetes,  2009, 58(3), 609-619.
 [http://dx.doi.org/10.2337/db08-1180] [PMID: 19073771]

[32]
Schneider, JA; Logan, SK Revisiting the role of Wnt/β-catenin signaling in prostate cancer. Mol. Cell. Endocrinol.,  2018, 462(Pt A), 3-8.

[33]
Baseggio, A.M.; Nuñez, C.E.C.; Dragano, N.R.V.; Lamas, C.A.; Braga, P.A.C.; Lenquiste, S.A.; Reyes, F.G.R.; Cagnon, V.H.A.; Júnior, M.R.M. Jaboticaba peel extract decrease autophagy in white adipose tissue and prevents metabolic disorders in mice fed with a high-fat diet. PharmaNutrition,  2018, 6(4), 147-156.
 [http://dx.doi.org/10.1016/j.phanu.2018.06.006]

[34]
Leite-Legatti, A.V.; Batista, Â.G.; Dragano, N.R.V.; Marques, A.C.; Malta, L.G.; Riccio, M.F.; Eberlin, M.N.; Machado, A.R.T.; de Carvalho-Silva, L.B.; Ruiz, A.L.T.G.; de Carvalho, J.E.; Pastore, G.M.; Maróstica, M.R. Jaboticaba peel: Antioxidant compounds, antiproliferative and antimutagenic activities. Food Res. Int.,  2012, 49(1), 596-603.
 [http://dx.doi.org/10.1016/j.foodres.2012.07.044]

[35]
Batista, Â.G.; Lenquiste, S.A.; Cazarin, C.B.B.; da Silva, J.K.; Luiz-Ferreira, A.; Bogusz, S., Jr; Wang, Hantao L.; de Souza, R.N.; Augusto, F.; Prado, M.A.; Maróstica, M.R., Jr Intake of jaboticaba peel attenuates oxidative stress in tissues and reduces circulating saturated lipids of rats with high-fat diet-induced obesity. J. Funct. Foods,  2014, 6, 450-461.
 [http://dx.doi.org/10.1016/j.jff.2013.11.011]

[36]
Lamas, C.A.; Lenquiste, S.A.; Baseggio, A.M.; Cuquetto-Leite, L.; Kido, L.A.; Aguiar, A.C.; Erbelin, M.N.; Collares-Buzato, C.B.; Maróstica, M.R., Jr; Cagnon, V.H.A. Jaboticaba extract prevents prediabetes and liver steatosis in high-fat-fed aging mice. J. Funct. Foods,  2018, 47, 434-446.
 [http://dx.doi.org/10.1016/j.jff.2018.06.005]

[37]
Lenquiste, S.A.; Marineli, R.S.; Moraes, É.A.; Dionísio, A.P.; Brito, E.S.; Maróstica, M.R. Jaboticaba peel and jaboticaba peel aqueous extract shows in vitro and in vivo antioxidant properties in obesity model. Food Res. Int.,  2015, 77, 162-170.
 [http://dx.doi.org/10.1016/j.foodres.2015.07.023]

[38]
Nogueira-Lima, E. Lamas, CdA.; Baseggio, AM.; do Vale, JSF.; Maróstica Junior, MR.; Cagnon, VHA. High-fat diet effects on the prostatic adenocarcinoma model and jaboticaba peel extract intake: Protective response in metabolic disorders and liver histopathology. Nutr. Cancer,  2019, 7, 1-12.

[39]
Jang, Y.G.; Go, R.E.; Hwang, K.A.; Choi, K.C. Resveratrol inhibits DHT-induced progression of prostate cancer cell line through interfering with the AR and CXCR4 pathway. J. Steroid Biochem. Mol. Biol.,  2019, 192, 105406.
 [http://dx.doi.org/10.1016/j.jsbmb.2019.105406] [PMID: 31185279]

[40]
Jordan, B.C.; Mock, C.D.; Thilagavathi, R.; Selvam, C. Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment. Life Sci.,  2016, 152, 135-144.
 [http://dx.doi.org/10.1016/j.lfs.2016.03.036] [PMID: 27018446]

[41]
Costea, T.; Nagy, P.; Ganea, C.; Szöllősi, J.; Mocanu, M.M. Molecular mechanisms and bioavailability of polyphenols in prostate cancer. Int. J. Mol. Sci.,  2019, 20(5), 1062.
 [http://dx.doi.org/10.3390/ijms20051062] [PMID: 30823649]

[42]
Lamas, C.A.; Kido, L.A.; Montico, F.; Collares-Buzato, C.B.; Maróstica, M.R.; Cagnon, V.H.A. A jaboticaba extract prevents prostatic damage associated with aging and high-fat diet intake. Food Funct.,  2020, 11(2), 1547-1559.
 [http://dx.doi.org/10.1039/C9FO02621E] [PMID: 32003372]

[43]
Lamas, C.A.; Kido, L.A.; Hermes, T.A.; Nogueira-Lima, E.; Minatel, E. Collares-Buzato, CB Brazilian berry extract (Myrciaria jaboticaba): A promising therapy to minimize prostatic inflammation and oxidative stress. The Prostate,  2020, 80(11)

[44]
Reeves, P.G.; Nielsen, F.H.; Fahey, G.C., Jr AIN-93 purified diets for laboratory rodents: Final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J. Nutr.,  1993, 123(11), 1939-1951.
 [http://dx.doi.org/10.1093/jn/123.11.1939] [PMID: 8229312]

[45]
Goena, M.; Marzo, F.; Fernández-González, A.L.; Tosar, A.; Frühbeck, G.; Santidrián, S. Effect of the raw legume Vicia ervilia on muscle and liver protein metabolism in growing rats. Rev. Esp. Fisiol.,  1989, 45(Suppl.), 55-59.
 [PMID: 2484317]

[46]
Lenquiste, S.A.; Batista, Â.G.; Marineli, R.S.; Dragano, N.R.V.; Maróstica, M.R. Jr Freeze-dried jaboticaba peel added to high-fat diet increases HDL-cholesterol and improves insulin resistance in obese rats. Food Res. Int.,  2012, 49(1), 153-160.
 [http://dx.doi.org/10.1016/j.foodres.2012.07.052]

[47]
Maróstica, M.R. Junior; Quitete, V.H.A.C.; Lamas, C.A.; Lenquiste, S.A.; Reyes, F.G.; Braga, P.A.C.; Baseggio, A.M. inventors; Instituto nacional da propriedade industrial, assignee. Composition comprising jabuticaba extract, and its use. Brasil patent BR 1020170054624, 2017.

[48]
Montico, F.; Hetzl, A.C.; Candido, E.M.; Favaro, W.J.; Cagnon, V.H. Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules. Micron,  2011, 42(6), 642-655.

[49]
da Silva, R.F.; Nogueira-Pangrazi, E.; Kido, L.A.; Montico, F.; Arana, S.; Kumar, D.; Raina, K.; Agarwal, R.; Cagnon, V.H.A. Nintedanib antiangiogenic inhibitor effectiveness in delaying adenocarcinoma progression in transgenic adenocarcinoma of the mouse prostate (TRAMP). J. Biomed. Sci.,  2017, 24(1), 31.
 [http://dx.doi.org/10.1186/s12929-017-0334-z] [PMID: 28499383]

[50]
Nogueira Pangrazi, E.; da Silva, R.F.; Kido, L.A.; Montico, F.; Cagnon, V.H.A. Nintedanib treatment delays prostate dorsolateral lobe cancer progression in the TRAMP model: Contribution to the epithelial‐stromal interaction balance. Cell Biol. Int.,  2018, 42(2), 153-168.
 [http://dx.doi.org/10.1002/cbin.10881] [PMID: 28980742]

[51]
Berman-Booty, L.D.; Sargeant, A.M.; Rosol, T.J.; Rengel, R.C.; Clinton, S.K.; Chen, C.S.; Kulp, S.K. A review of the existing grading schemes and a proposal for a modified grading scheme for prostatic lesions in TRAMP mice. Toxicol. Pathol.,  2012, 40(1), 5-17.
 [http://dx.doi.org/10.1177/0192623311425062] [PMID: 22021166]

[52]
Gingrich, J.R.; Barrios, R.J.; Foster, B.A.; Greenberg, N.M. Pathologic progression of autochthonous prostate cancer in the TRAMP model. Prostate Cancer Prostatic Dis.,  1999, 2(2), 70-75.
 [http://dx.doi.org/10.1038/sj.pcan.4500296] [PMID: 12496841]

[53]
Kido, L.A.; Hetzl, A.C.; Cândido, E.M.; Montico, F.; Lorencini, R.M.; Cagnon, V.H.A. Antiangiogenic and finasteride therapies: Responses of the prostate microenvironment in elderly mice. Life Sci.,  2014, 106(1-2), 58-70.
 [http://dx.doi.org/10.1016/j.lfs.2014.04.027] [PMID: 24792519]

[54]
Montico, F.; Kido, L.A.; Hetzl, A.C.; Lorencini, R.M.; Cândido, E.M.; Cagnon, V.H.A. Antiangiogenic therapy effects on age-associated matrix metalloproteinase-9 (MMP-9) and insulin-like growth factor receptor-1 (IGFR-1) responses: A comparative study of prostate disorders in aged and TRAMP mice. Histochem. Cell Biol.,  2014, 142(3), 269-284.
 [http://dx.doi.org/10.1007/s00418-014-1193-2] [PMID: 24562790]

[55]
Weidner, N.; Carroll, P.R.; Flax, J.; Blumenfeld, W.; Folkman, J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am. J. Pathol.,  1993, 143(2), 401-409.
 [PMID: 7688183]

[56]
Hochberg, D.A.; Basillote, J.B.; Armenakas, N.A.; Vasovic, L.; Shevchuk, M.; Pareek, G.; Fracchia, J.A. Decreased suburethral prostatic microvessel density in finasteride treated prostates: A possible mechanism for reduced bleeding in benign prostatic hyperplasia. J. Urol.,  2002, 167(4), 1731-1733.
 [http://dx.doi.org/10.1016/S0022-5347(05)65188-9] [PMID: 11912398]

[57]
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem.,  1979, 95(2), 351-358.
 [http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]

[58]
Hadwan, M.H.; Abed, H.N. Data supporting the spectrophotometric method for the estimation of catalase activity. Data Brief,  2016, 6, 194-199.
 [http://dx.doi.org/10.1016/j.dib.2015.12.012] [PMID: 26862558]

[59]
Winterbourn, C.C.; Hawkins, R.E.; Brian, M.; Carrell, R.W. The estimation of red cell superoxide dismutase activity. J. Lab. Clin. Med.,  1975, 85(2), 337-341.
 [PMID: 803541]

[60]
Fijnvandraat, A.C.; De Boer, P.A.J.; Deprez, R.H.L.; Moorman, A.F.M. Non‐radioactive in situ detection of mRNA in ES cell‐derived cardiomyocytes and in the developing heart. Microsc. Res. Tech.,  2002, 58(5), 387-394.
 [http://dx.doi.org/10.1002/jemt.10154] [PMID: 12226808]

[61]
Lewis, M.E.; Sherman, T.G.; Watson, S.J. In situ hybridization histochemistry with synthetic oligonucleotides: Strategies and methods. Peptides,  1985, 6(Suppl. 2), 75-87.
 [http://dx.doi.org/10.1016/0196-9781(85)90138-X] [PMID: 4080619]

[62]
Zar, J. Biostatistical analysis. 4th New Jersey; Prentice Hall, 1999. 

[63]
Mezni, A.; Aoua, H.; Khazri, O.; Limam, F.; Aouani, E. Lithium induced oxidative damage and inflammation in the rat’s heart: Protective effect of grape seed and skin extract. Biomed. Pharmacother.,  2017, 95, 1103-1111.

[64]
Wang, Y.; Xiang, L.; Wang, C.; Tang, C.; He, X. Antidiabetic and antioxidant effects and phytochemicals of mulberry fruit (Morus alba L.) polyphenol enhanced extract. PLoS One,  2013, 8(7), e71144.
 [http://dx.doi.org/10.1371/journal.pone.0071144] [PMID: 23936259]

[65]
Fraga, C.G.; Galleano, M.; Verstraeten, S.V.; Oteiza, P.I. Basic biochemical mechanisms behind the health benefits of polyphenols. Mol. Aspects Med.,  2010, 31(6), 435-445.
 [http://dx.doi.org/10.1016/j.mam.2010.09.006] [PMID: 20854840]

[66]
Hussain, T.; Tan, B.; Yin, Y.; Blachier, F.; Tossou, M.C.B.; Rahu, N. Oxidative stress and inflammation: What polyphenols can do for us? Oxid. Med. Cell. Longev.,  2016, 2016, 1-9.
 [http://dx.doi.org/10.1155/2016/7432797] [PMID: 27738491]

[67]
Oteiza, P.I.; Erlejman, A.G.; Verstraeten, S.V.; Keen, C.L.; Fraga, C.G. Flavonoid-membrane interactions: A protective role of flavonoids at the membrane surface? Clin. Dev. Immunol.,  2005, 12(1), 19-25.
 [http://dx.doi.org/10.1080/10446670410001722168] [PMID: 15712595]

[68]
Sharmila, G.; Bhat, F.A.; Arunkumar, R.; Elumalai, P.; Raja Singh, P.; Senthilkumar, K.; Arunakaran, J. Chemopreventive effect of quercetin, a natural dietary flavonoid on prostate cancer in in vivo model. Clin. Nutr.,  2014, 33(4), 718-726.
 [http://dx.doi.org/10.1016/j.clnu.2013.08.011]

[69]
Montico, F.; Kido, L.A.; San Martin, R.; Rowley, D.R.; Cagnon, V.H.A. Reactive stroma in the prostate during late life: The role of microvasculature and antiangiogenic therapy influences. Prostate,  2015, 75(14), 1643-1661.
 [http://dx.doi.org/10.1002/pros.23045] [PMID: 26184673]

[70]
Chen, H.S.; Bai, M.H.; Zhang, T.; Li, G.D.; Liu, M. Ellagic acid induces cell cycle arrest and apoptosis through TGF-β/Smad3 signaling pathway in human breast cancer MCF-7 cells. Int. J. Oncol.,  2015, 46(4), 1730-1738.
 [http://dx.doi.org/10.3892/ijo.2015.2870] [PMID: 25647396]

[71]
Tripathi, M.; Nandana, S.; Yamashita, H.; Ganesan, R.; Kirchhofer, D.; Quaranta, V. Laminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression. J. Biol. Chem.,  2008, 283(45), 30576-30584.
 [http://dx.doi.org/10.1074/jbc.M802312200] [PMID: 18784072]

[72]
Bair, E.L.; Chen, M.L.; McDaniel, K.; Sekiguchi, K.; Cress, A.E.; Nagle, R.B.; Bowden, G.T. Membrane type 1 matrix metalloprotease cleaves laminin-10 and promotes prostate cancer cell migration. Neoplasia,  2005, 7(4), 380-389.
 [http://dx.doi.org/10.1593/neo.04619] [PMID: 15967115]

[73]
Herman, J.G.; Stadelman, H.L.; Roselli, C.E. Curcumin blocks CCL2-induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity. Int. J. Oncol.,  2009, 34(5), 1319-1327.
 [PMID: 19360344]

[74]
Deb, G.; Shankar, E.; Thakur, V.S.; Ponsky, L.E.; Bodner, D.R.; Fu, P.; Gupta, S. Green tea–induced epigenetic reactivation of tissue inhibitor of matrix metalloproteinase‐3 suppresses prostate cancer progression through histone‐modifying enzymes. Mol. Carcinog.,  2019, 58(7), 1194-1207.
 [http://dx.doi.org/10.1002/mc.23003] [PMID: 30854739]

[75]
Ferruelo, A.; de las Heras, M.M.; Redondo, C.; Ramón de Fata, F.; Romero, I.; Angulo, J.C. Wine polyphenols exert their antineoplastic effect on the androgen-resistant PC-3 cell line through the inhibition of the transcriptional activity of the COX-2 promoter mediated by NF-kβ. Actas Urol. Esp.,  2014, 38(7), 429-437.
 [http://dx.doi.org/10.1016/j.acuro.2014.02.017] [PMID: 24836925]

[76]
Kampa, M.; Hatzoglou, A.; Notas, G.; Damianaki, A.; Bakogeorgou, E.; Gemetzi, C.; Kouroumalis, E.; Martin, P.M.; Castanas, E. Wine antioxidant polyphenols inhibit the proliferation of human prostate cancer cell lines. Nutr. Cancer,  2000, 37(2), 223-233.
 [http://dx.doi.org/10.1207/S15327914NC372_16] [PMID: 11142097]

[77]
Vital, P.; Castro, P.; Ittmann, M. Oxidative stress promotes benign prostatic hyperplasia. Prostate,  2016, 76(1), 58-67.
 [http://dx.doi.org/10.1002/pros.23100] [PMID: 26417670]

[78]
Shukla, S.; MacLennan, G.T.; Fu, P.; Gupta, S. Apigenin attenuates insulin-like growth factor-I signaling in an autochthonous mouse prostate cancer model. Pharm. Res.,  2012, 29(6), 1506-1517.
 [http://dx.doi.org/10.1007/s11095-011-0625-0] [PMID: 22139534]

[79]
Lall, R.; Syed, D.; Adhami, V.; Khan, M.; Mukhtar, H. Dietary polyphenols in prevention and treatment of prostate cancer. Int. J. Mol. Sci.,  2015, 16(2), 3350-3376.
 [http://dx.doi.org/10.3390/ijms16023350] [PMID: 25654230]

[80]
Zhou, Y.; Zheng, J.; Li, Y.; Xu, D.P.; Li, S.; Chen, Y.M.; Li, H.B. Natural polyphenols for prevention and treatment of cancer. Nutrients,  2016, 8(8), 515.
 [http://dx.doi.org/10.3390/nu8080515] [PMID: 27556486]

[81]
Adhami, V.M.; Siddiqui, I.A.; Ahmad, N.; Gupta, S.; Mukhtar, H. Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer. Cancer Res.,  2004, 64(23), 8715-8722.
 [http://dx.doi.org/10.1158/0008-5472.CAN-04-2840] [PMID: 15574782]

[82]
Li, W.W.; Li, V.W.; Hutnik, M.; Chiou, A.S. Tumor angiogenesis as a target for dietary cancer prevention. J. Oncol.,  2012, 2012, 1-23.
 [http://dx.doi.org/10.1155/2012/879623] [PMID: 21977033]

[83]
He, Z.; Chen, A.; Rojanasakul, Y.; Rankin, G.O.; Chen, Y.C. Gallic acid, a phenolic compound, exerts anti-angiogenic effects via the PTEN/AKT/HIF-1α/VEGF signaling pathway in ovarian cancer cells. Oncol. Rep.,  2016, 35(1), 291-297.
 [http://dx.doi.org/10.3892/or.2015.4354] [PMID: 26530725]

[84]
Yau, T.O.; Chan, C.Y.; Chan, K.L.; Lee, M.F.; Wong, C.M.; Fan, S.T.; Ng, I.O.L. HDPR1, a novel inhibitor of the WNT/β-catenin signaling, is frequently downregulated in hepatocellular carcinoma: involvement of methylation-mediated gene silencing. Oncogene,  2005, 24(9), 1607-1614.
 [http://dx.doi.org/10.1038/sj.onc.1208340] [PMID: 15580286]

[85]
Cheng, H.; Deng, Z.; Wang, Z.; Zhang, W.; Su, J. The role of aberrant promoter hypermethylation of DACT1 in bladder urothelial carcinoma. J. Biomed. Res.,  2012, 26(5), 319-324.
 [http://dx.doi.org/10.7555/JBR.26.20110099] [PMID: 23554767]

[86]
Shtutman, M.; Zhurinsky, J.; Simcha, I.; Albanese, C.; D’Amico, M.; Pestell, R.; Ben-Ze’ev, A. The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway. Proc. Natl. Acad. Sci. USA,  1999, 96(10), 5522-5527.
 [http://dx.doi.org/10.1073/pnas.96.10.5522] [PMID: 10318916]

[87]
Schmidt, E.V. The role of c-myc in regulation of translation initiation. Oncogene,  2004, 23(18), 3217-3221.
 [http://dx.doi.org/10.1038/sj.onc.1207548] [PMID: 15094771]

[88]
Soleimani, M.; Homayoun, M.; Ghasemnezhad Targhi, R. Anti-proliferative and anti-apoptotic effects of grape seed extract on chemo-resistant OVCAR-3 ovarian cancer cells. Res. Pharm. Sci.,  2020, 15(4), 390-400.
 [http://dx.doi.org/10.4103/1735-5362.293517] [PMID: 33312217]

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DOI https://dx.doi.org/10.2174/0122103155281770240104091620	Print ISSN 2210-3155
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