Dietary Tomato or Lycopene Do Not Reduce Castration-Resistant Prostate Cancer Progression in a Murine Model.

BACKGROUND Dietary tomato products or lycopene protect against prostate carcinogenesis, but their impact on the emergence of castration-resistant prostate cancer (CRPC) is unknown. OBJECTIVE We hypothesized that tomato or lycopene products would reduce the emergence of CRPC. METHODS Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were castrated at 12-13 wk and the emergence of CRPC was monitored by ultrasound in each study. In Study 1, TRAMP mice (n = 80) were weaned onto an AIN-93G-based control diet (Con-L, n = 28), a 10% tomato powder diet (TP-L, 10% lyophilized w/w, n = 26), or a control diet followed by a tomato powder diet after castration (TP-Int1, n = 26). In Study 2, TRAMP mice (n = 85) were randomized onto a control diet with placebo beadlets (Con-Int, n = 29), a tomato diet with placebo beadlets (TP-Int2, n = 29), or a control diet with lycopene beadlets (Lyc-Int, n = 27) following castration (aged 12 wk). Tumor incidence and growth were monitored by ultrasound beginning at an age of 10 wk. Mice were euthanized 4 wk after tumor detection or aged 30 wk if no tumor was detected. Tissue weights were compared by ANOVA followed by Dunnett's test. Tumor volumes were compared using generalized linear mixed model regression. RESULTS Ultrasound estimates for the in vivo tumor volume were strongly correlated with tumor weight at necropsy (R2 = 0.75 and 0.94, P <0.001 for both Studies 1 and 2, respectively). Dietary treatments after castration did not significantly impact cancer incidence, time to tumor detection, or final tumor weight. CONCLUSIONS In contrast to studies of de novo carcinogenesis in multiple preclinical models, tomato components had no significant impact on the emergence of CRPC in the TRAMP model. It is possible that specific mutant subclones of prostate cancer may continue to show some antiproliferative response to tomato components, but further studies are needed to confirm this.

[1]  N. Gupta,et al.  A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer , 2003, BJU international.

[2]  F. Hu,et al.  The 2015 Dietary Guidelines Advisory Committee Scientific Report: Development and Major Conclusions. , 2016, Advances in nutrition.

[3]  G. Young,et al.  β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model , 2016, Cancer Prevention Research.

[4]  D. Pearl,et al.  Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis , 2014, Cancer Prevention Research.

[5]  M. Loda,et al.  Dietary lycopene, angiogenesis, and prostate cancer: a prospective study in the prostate-specific antigen era. , 2014, Journal of the National Cancer Institute.

[6]  J. Erdman,et al.  Combined consumption of soy germ and tomato powders results in altered isoflavone and carotenoid bioavailability in rats. , 2011, Journal of agricultural and food chemistry.

[7]  J. Erdman,et al.  Processed and raw tomato consumption and risk of prostate cancer: a systematic review and dose–response meta-analysis , 2018, Prostate Cancer and Prostatic Diseases.

[8]  R. Hoover,et al.  Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies. , 2015, The American journal of clinical nutrition.

[9]  J. Erdman,et al.  Can Lycopene Impact the Androgen Axis in Prostate Cancer?: A Systematic Review of Cell Culture and Animal Studies , 2019, Nutrients.

[10]  G. Lesinski,et al.  Enhanced bioavailability of lycopene when consumed as cis-isomers from tangerine compared to red tomato juice, a randomized, cross-over clinical trial. , 2015, Molecular nutrition & food research.

[11]  M. Lilly,et al.  Lycopene enhances docetaxel's effect in castration-resistant prostate cancer associated with insulin-like growth factor I receptor levels. , 2011, Neoplasia.

[12]  Aaron Fenster,et al.  A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model. , 2005, Cancer research.

[13]  K. Christov,et al.  Effects of Tomato Sauce Consumption on Apoptotic Cell Death in Prostate Benign Hyperplasia and Carcinoma , 2003, Nutrition and cancer.

[14]  Tsuey-Ming Chen,et al.  Pathobiology of autochthonous prostate cancer in a pre‐clinical transgenic mouse model , 2003, The Prostate.

[15]  R. V. van Breemen,et al.  Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention. , 2001, Journal of the National Cancer Institute.

[16]  John R. Stevens,et al.  A comparison of multiple testing adjustment methods with block-correlation positively-dependent tests , 2017, PloS one.

[17]  A. Belldegrun,et al.  Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. , 1999, Cancer research.

[18]  C. Huggins Prostatic cancer treated by orchiectomy; the five year results. , 1946, Journal of the American Medical Association.

[19]  P. Borel,et al.  Lycopene bioavailability is associated with a combination of genetic variants. , 2015, Free radical biology & medicine.

[20]  C. Fairman,et al.  Effects of a Group-Mediated Exercise and Dietary Intervention in the Treatment of Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: Results From the IDEA-P Trial. , 2018, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[21]  K. Iczkowski,et al.  Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles , 2016, Oncotarget.

[22]  Chih-min Yang,et al.  Growth inhibitory efficacy of lycopene and β-carotene against androgen-independent prostate tumor cells xenografted in nude mice. , 2011, Molecular nutrition & food research.

[23]  Lawrence D. True,et al.  Integrative Clinical Genomics of Advanced Prostate Cancer , 2015, Cell.

[24]  S. Roth,et al.  Lycopene for advanced hormone refractory prostate cancer: a prospective, open phase II pilot study. , 2009, The Journal of urology.

[25]  M. Banerjee,et al.  Lycopene and Soy Isoflavones in the Treatment of Prostate Cancer , 2007, Nutrition and cancer.

[26]  P. Bowen,et al.  Role of lycopene and tomato products in prostate health. , 2005, Biochimica et biophysica acta.

[27]  M. Katsogiannou,et al.  The hallmarks of castration-resistant prostate cancers. , 2015, Cancer treatment reviews.

[28]  D. Robins,et al.  Profiling Human Androgen Receptor Mutations Reveals Treatment Effects in a Mouse Model of Prostate Cancer , 2008, Molecular Cancer Research.

[29]  A. Jemal,et al.  Annual Report to the Nation on the Status of Cancer, Featuring Cancer in Men and Women Age 20–49 Years , 2019, Journal of the National Cancer Institute.

[30]  M. Rafi,et al.  Lycopene modulates growth and survival associated genes in prostate cancer. , 2013, The Journal of nutritional biochemistry.

[31]  J. Erdman,et al.  Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis , 2017, Prostate Cancer and Prostatic Diseases.

[32]  K. Rowland,et al.  A tomato-based, lycopene-containing intervention for androgen-independent prostate cancer: results of a Phase II study from the North Central Cancer Treatment Group. , 2007, Urology.

[33]  G. Attard Anti-androgen monotherapy for metastatic prostate cancer. , 2014, The Lancet. Oncology.

[34]  K. Swanson,et al.  Review of animal models in carotenoid research. , 1999, The Journal of nutrition.

[35]  R. Hayes,et al.  Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites. , 2002, American journal of epidemiology.

[36]  C. Huggins,et al.  Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate , 1941, CA: a cancer journal for clinicians.

[37]  R. Abaza,et al.  A Novel Tomato-Soy Juice Induces a Dose-Response Increase in Urinary and Plasma Phytochemical Biomarkers in Men with Prostate Cancer. , 2018, The Journal of nutrition.

[38]  S. Mayne,et al.  Lessons learned from randomized clinical trials of micronutrient supplementation for cancer prevention. , 2012, Annual review of nutrition.

[39]  S. Mayne Oxidative Stress, Dietary Antioxidant Supplements, and Health: Is the Glass Half Full or Half Empty? , 2013, Cancer Epidemiology, Biomarkers & Prevention.

[40]  J. Erdman,et al.  Compartmental and noncompartmental modeling of ¹³C-lycopene absorption, isomerization, and distribution kinetics in healthy adults. , 2015, The American journal of clinical nutrition.

[41]  A. Toland,et al.  Single Nucleotide Polymorphisms in β-Carotene Oxygenase 1 are Associated with Plasma Lycopene Responses to a Tomato-Soy Juice Intervention in Men with Prostate Cancer. , 2019, The Journal of nutrition.

[42]  H. Beydoun,et al.  Associations of serum vitamin A and carotenoid levels with markers of prostate cancer detection among US men , 2011, Cancer Causes & Control.

[43]  J. Erdman,et al.  The Interactions of Dietary Tomato Powder and Soy Germ on Prostate Carcinogenesis in the TRAMP Model , 2013, Cancer Prevention Research.

[44]  J. Erdman,et al.  Low-lycopene containing tomato powder diet does not protect against prostate cancer in TRAMP mice. , 2015, Nutrition research.

[45]  S. Kulp,et al.  A Review of the Existing Grading Schemes and a Proposal for a Modified Grading Scheme for Prostatic Lesions in TRAMP Mice , 2012, Toxicologic pathology.

[46]  M. Banerjee,et al.  Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[47]  R. Borojevic,et al.  Influence of Lycopene on Cell Viability, Cell Cycle, and Apoptosis of Human Prostate Cancer and Benign Hyperplastic Cells , 2013, Nutrition and cancer.

[48]  Nihal Ahmad,et al.  Dose translation from animal to human studies revisited , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[49]  S. Clinton,et al.  A comparison of plasma and prostate lycopene in response to typical servings of tomato soup, sauce or juice in men before prostatectomy , 2015, British Journal of Nutrition.

[50]  T. Jin,et al.  Lycopene inhibits the growth of human androgen-independent prostate cancer cells in vitro and in BALB/c nude mice. , 2005, The Journal of nutrition.

[51]  M. Vasson,et al.  Differential effects of lycopene consumed in tomato paste and lycopene in the form of a purified extract on target genes of cancer prostatic cells. , 2010, The American journal of clinical nutrition.

[52]  M. Kattan,et al.  Androgen-independent prostate cancer progression in the TRAMP model. , 1997, Cancer research.

[53]  D. Bostwick,et al.  cis-trans lycopene isomers, carotenoids, and retinol in the human prostate. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[54]  E. Domany,et al.  Interspecies Comparison of Prostate Cancer Gene-expression Profiles Reveals Genes Associated with Aggressivetumors , 2022 .

[55]  S. Lemeshow,et al.  Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. , 2004, Journal of the National Cancer Institute.

[56]  M. Rubin,et al.  Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses , 2018, Nature Communications.