Nexrutine and exercise similarly prevent high grade prostate tumors in transgenic mouse model
Autoři:
Darpan I. Patel aff001; Kira Abuchowski aff001; Roble Bedolla aff004; Paul Rivas aff004; Nicolas Musi aff003; Robert Reddick aff005; A. Pratap Kumar aff002
Působiště autorů:
School of Nursing, UT Health San Antonio, San Antonio, Texas, United States of America
aff001; Mays Cancer Center at UT Health San Antonio, San Antonio, Texas, United States of America
aff002; Sam and Ann Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, Texas, United States of America
aff003; Department of Urology, School of Medicine, UT Health San Antonio, San Antonio, Texas, United States of America
aff004; Department of Pathology, School of Medicine, UT Health San Antonio, San Antonio, Texas, United States of America
aff005
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0226187
Souhrn
The purpose of this investigation was to compare the antitumorigenic effects of the natural product Nexrutine to voluntary wheel running (VWR) in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Forty-five, 10-week old TRAMP mice were randomized to either receive free access to the running wheel, Nexrutine pelleted into chow at 600 mg/kg or no treatment control. Mice were serially sacrificed at weeks 4, 8,12 and 20 weeks. Palpable tumors, body weight, food consumption and running wheel activity were monitored weekly. At necropsy, tumors and serum were harvested and stored for analysis. Serum was used to quantify circulating cytokines in 4 and 20 week time points. Nexrutine supplementation led to a 66% protection against high grade tumors. Exercise resulted in a 60% protection against high grade tumors. Both interventions reduced concentrations of IL-1α. Exercise also significantly lowered concentrations of eotaxin, IL-5, IL-12(p40) and VEGF. While there were no significant differences at baseline, exercise mice had significantly lower IL-5 and VEGF compared to control at the 20 week time point. Nexrutine also significantly reduced circulating IL-9 concentrations. No significant differences were observed when compared to the control group. Immunohistochemistry of tumor sections showed significantly lower expression of pAkt in Nexrutine fed mice with no visible differences for NFκB. In conclusion, both Nexrutine and exercise suppressed tumor growth. Though similar outcomes were seen in this comparative effectiveness study, the mechanisms by which exercise and Nexrutine exert this benefit may focus on different pathways.
Klíčová slova:
Cytokines – Mouse models – Exercise – Cell staining – Running – Prostate cancer – Prostate gland – Differentiated tumors
Zdroje
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians. 2016;66(1):7–30.
2. Haas GP, Delongchamps N, Brawley OW, Wang CY, de la Roza G. The Worldwide Epidemiology of Prostate Cancer: Perspectives from Autopsy Studies. The Canadian journal of urology. 2008;15(1):3866–71. 18304396
3. Norat T, Aune D, Chan D, Romaguera D. Fruits and vegetables: updating the epidemiologic evidence for the WCRF/AICR lifestyle recommendations for cancer prevention. Advances in nutrition and cancer: Springer; 2014. p. 35–50.
4. Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV, et al. American Cancer Society guidelines on nutrition and physical activity for cancer prevention. CA: a cancer journal for clinicians. 2012;62(1):30–67.
5. Yang M, Kenfield SA, Van Blarigan EL, Batista JL, Sesso HD, Ma J, et al. Dietary patterns after prostate cancer diagnosis in relation to disease-specific and total mortality. Cancer prevention research. 2015;8(6):545–51. doi: 10.1158/1940-6207.CAPR-14-0442 26031631
6. Beydoun N, Bucci JA, Chin YS, Spry N, Newton R, Galvao DA. Prospective study of exercise intervention in prostate cancer patients on androgen deprivation therapy. J Med Imaging Radiat Oncol. 2013. Epub 2013/10/15. doi: 10.1111/1754-9485.12115 24118798.
7. Galvao DA, Nosaka K, Taaffe DR, Spry N, Kristjanson LJ, McGuigan MR, et al. Resistance training and reduction of treatment side effects in prostate cancer patients. Medicine and science in sports and exercise. 2006;38(12):2045–52. Epub 2006/12/06. doi: 10.1249/01.mss.0000233803.48691.8b 17146309.
8. Galvao DA, Taaffe DR, Spry N, Joseph D, Newton RU. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol. 2010;28(2):340–7. Epub 2009/12/02. doi: 10.1200/JCO.2009.23.2488 19949016.
9. Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovish CF. Resistance exercise decreases skeletal muscle tumor necrosis factor α in frail elderly humans. The FASEB Journal. 2001;15(2):475–82. doi: 10.1096/fj.00-0274com 11156963
10. Monga U, Garber SL, Thornby J, Vallbona C, Kerrigan AJ, Monga TN, et al. Exercise Prevents Fatigue and Improves Quality of Life in Prostate Cancer Patients Undergoing Radiotherapy. Archives of physical medicine and rehabilitation. 2007;88(11):1416–22. doi: 10.1016/j.apmr.2007.08.110 17964881
11. Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2003;21(9):1653–9. Epub 2003/05/02. doi: 10.1200/JCO.2003.09.534 12721238.
12. Windsor PM, Nicol KF, Potter J. A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma. Cancer. 2004;101(3):550–7. Epub 2004/07/27. doi: 10.1002/cncr.20378 15274068.
13. Shephard RJ. Physical activity and prostate cancer: an updated review. Sports Medicine. 2017;47(6):1055–73. doi: 10.1007/s40279-016-0648-0 27844337
14. Singh AA, Jones LW, Antonelli JA, Gerber L, Calloway EE, Shuler KH, et al. Association between exercise and primary incidence of prostate cancer. Cancer. 2013;119(7):1338–43. doi: 10.1002/cncr.27791 23401030
15. Antonelli JA, Jones LW, Bañez LL, Thomas J-A, Anderson K, Taylor LA, et al. Exercise and prostate cancer risk in a cohort of veterans undergoing prostate needle biopsy. The Journal of urology. 2009;182(5):2226–31. doi: 10.1016/j.juro.2009.07.028 19758620
16. De Nunzio C, Presicce F, Lombardo R, Cancrini F, Petta S, Trucchi A, et al. Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis. BJU international. 2016;117(6B).
17. Kenfield SA, Stampfer MJ, Giovannucci E, Chan JM. Physical Activity and Survival After Prostate Cancer Diagnosis in the Health Professionals Follow-Up Study. Journal of Clinical Oncology. 2011;29(6):726–32. doi: 10.1200/JCO.2010.31.5226 21205749
18. Richman EL, Kenfield SA, Stampfer MJ, Paciorek A, Carroll PR, Chan JM. Physical activity after diagnosis and risk of prostate cancer progression: data from the cancer of the prostate strategic urologic research endeavor. Cancer research. 2011.
19. Friedenreich CM, Wang Q, Neilson HK, Kopciuk KA, McGregor SE, Courneya KS. Physical activity and survival after prostate cancer. European urology. 2016;70(4):576–85. doi: 10.1016/j.eururo.2015.12.032 26774959
20. Zheng X, Cui XX, Huang MT, Liu Y, Shih WJ, Lin Y, et al. 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. 2008;19(6):1583–8. Epub 2008/05/24. 18497969
21. Zheng X, Cui XX, Huang MT, Liu Y, Wagner GC, Lin Y, et al. Inhibition of progression of androgen-dependent prostate LNCaP tumors to androgen independence in SCID mice by oral caffeine and voluntary exercise. Nutr Cancer. 2012;64(7):1029–37. Epub 2012/10/16. doi: 10.1080/01635581.2012.716899 23061906.
22. Andrianopoulos G, Nelson RL, Bombeck CT, Souza G. The influence of physical activity in 1,2 dimethylhydrazine induced colon carcinogenesis in the rat. Anticancer Res. 1987;7(4b):849–52. Epub 1987/07/01. 3674772.
23. Cohen LA, Choi K, Backlund JY, Harris R, Wang CX. Modulation of N-nitrosomethylurea induced mammary tumorigenesis by dietary fat and voluntary exercise. In Vivo. 1991;5(4):333–44. Epub 1991/07/01. 1810418.
24. Wannamethee SG, Shaper AG, Walker M. Physical activity and risk of cancer in middle-aged men. British journal of cancer. 2001;85(9):1311–6. Epub 2001/11/27. doi: 10.1054/bjoc.2001.2096 11720466.
25. Craven-Giles T, Tagliaferro AR, Ronan AM, Baumgartner KJ, Roebuck BD. Dietary modulation of pancreatic carcinogenesis: calories and energy expenditure. Cancer Res. 1994;54(7 Suppl):1964s–8s. Epub 1994/04/01. 8137321.
26. Roebuck BD, McCaffrey J, Baumgartner KJ. Protective effects of voluntary exercise during the postinitiation phase of pancreatic carcinogenesis in the rat. Cancer research. 1990;50(21):6811–6. Epub 1990/11/01. 2208145.
27. Esser KA, Harpole CE, Prins GS, Diamond AM. Physical activity reduces prostate carcinogenesis in a transgenic model. The Prostate. 2009;69(13):1372–7. Epub 2009/06/03. doi: 10.1002/pros.20987 19489028.
28. Blackwell DL, Clark TC. State variation in meeting the 2008 federal guidelines for both aerobic and muscle-strengthening activities through leisure-time physical activity among adults aged 18–64: United States 2010–2015. National Health Statistics Report. 2018;(112).
29. Barnard RJ, Leung PS, Aronson WJ, Cohen P, Golding LA. A mechanism to explain how regular exercise might reduce the risk for clinical prostate cancer. European Journal of Cancer Prevention. 2007;16(5):415–21. doi: 10.1097/01.cej.0000243851.66985.e4 17923812
30. Keogh JW, Shepherd D, Krageloh CU, Ryan C, Masters J, Shepherd G, et al. Predictors of physical activity and quality of life in New Zealand prostate cancer survivors undergoing androgen-deprivation therapy. N Z Med J. 2010;123(1325):20–9. Epub 2011/02/15. 21317957.
31. Bellizzi KM, Rowland JH, Jeffery DD, McNeel T. Health behaviors of cancer survivors: examining opportunities for cancer control intervention. J Clin Oncol. 2005;23(34):8884–93. Epub 2005/11/30. doi: 10.1200/JCO.2005.02.2343 16314649.
32. Coups EJ, Ostroff JS. A population-based estimate of the prevalence of behavioral risk factors among adult cancer survivors and noncancer controls. Prev Med. 2005;40(6):702–11. Epub 2005/04/27. doi: 10.1016/j.ypmed.2004.09.011 15850868.
33. Kumar AP, Graham H, Robson C, Thompson IM, Ghosh R. Natural products: potential for developing Phellodendron amurense bark extract for prostate cancer management. Mini Rev Med Chem. 2010;10(5):388–97. Epub 2010/04/08. doi: 10.2174/138955710791330936 20370708.
34. Kumar AP, Bhaskaran S, Ganapathy M, Crosby K, Davis MD, Kochunov P, et al. Akt/cAMP-responsive element binding protein/cyclin D1 network: a novel target for prostate cancer inhibition in transgenic adenocarcinoma of mouse prostate model mediated by Nexrutine, a Phellodendron amurense bark extract. Clinical cancer research: an official journal of the American Association for Cancer Research. 2007;13(9):2784–94. Epub 2007/05/03. doi: 10.1158/1078-0432.ccr-06-2974 17473212
35. Garcia GE, Nicole A, Bhaskaran S, Gupta A, Kyprianou N, Kumar AP. Akt-and CREB-mediated prostate cancer cell proliferation inhibition by Nexrutine, a Phellodendron amurense extract. Neoplasia. 2006;8(6):523–33. Epub 2006/07/06. doi: 10.1593/neo.05745 16820098
36. Ghosh R, Garcia GE, Crosby K, Inoue H, Thompson IM, Troyer DA, et al. Regulation of Cox-2 by cyclic AMP response element binding protein in prostate cancer: potential role for nexrutine. Neoplasia. 2007;9(11):893–9. doi: 10.1593/neo.07502 18030357
37. Ghosh R, Graham H, Rivas P, Tan XJ, Crosby K, Bhaskaran S, et al. Phellodendron amurense Bark Extract Prevents Progression of Prostate Tumors in Transgenic Adenocarcinoma of Mouse Prostate: Potential for Prostate Cancer Management. Anticancer Research. 2010;30(3):857–65. 20393007
38. Gingrich JR, Barrios RJ, Foster BA, Greenberg NM. Pathologic progression of autochthonous prostate cancer in the TRAMP model. Prostate Cancer Prostatic Dis. 1999;2(2):70–5. Epub 2002/12/24. doi: 10.1038/sj.pcan.4500296 12496841.
39. Hussain S, Patel D, Ghosh R, Kumar A. Extracting the Benefit of Nexrutine® for Cancer Prevention. Current Pharmacology Reports. 2015:1–8. doi: 10.1007/s40495-015-0029-7 26539341
40. Kumar A, Graham H, Robson C, Thompson I, Ghosh R. Natural products: potential for developing Phellodendron amurense bark extract for prostate cancer management. Mini reviews in medicinal chemistry. 2010;10(5):388–97. doi: 10.2174/138955710791330936 20370708
41. Kumar AP, Bhaskaran S, Ganapathy M, Crosby K, Davis MD, Kochunov P, et al. Akt/CREB/Cyclin D1 network: a novel target for prostate cancer inhibition in transgenic adenocarcinoma of mouse prostate (TRAMP) model mediated by Nexrutine®, a Phellodendron amurense bark extract. Clinical cancer research: an official journal of the American Association for Cancer Research. 2007;13(9):2784–94.
42. Glade MJ. World Cancer Research Fund/American Institute for Cancer ResearchFood, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective2007American Institute for Cancer ResearchWashington, D. CISBN: 978-0-9722522-2-5. Elsevier; 2008.
43. Swanson GP, Jones WE, Ha CS, Jenkins CA, Kumar AP, Basler J. Tolerance of Phellodendron amurense Bark Extract (Nexrutine®) in Patients with Human Prostate Cancer. Phytotherapy Research. 2015;29(1):40–2. doi: 10.1002/ptr.5221 25205619
44. Wekesa A, Harrison M, Watson R. Physical activity and its mechanistic effects on prostate cancer. Prostate cancer and prostatic diseases. 2015;18(3):197–207. doi: 10.1038/pcan.2015.9 25800589
45. Friedenreich C, McGregor S, Courneya K, Angyalfi S, Elliott F. Case-control study of lifetime total physical activity and prostate cancer risk. American journal of epidemiology. 2004;159(8):740–9. doi: 10.1093/aje/kwh106 15051583
46. McTiernan A. Mechanisms linking physical activity with cancer. Nature Reviews Cancer. 2008;8(3):205–11. doi: 10.1038/nrc2325 18235448
47. Gao J, Tian J, Lv Y, Shi F, Kong F, Shi H, et al. Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells. Cancer science. 2009;100(3):389–95. Epub 2009/01/22. doi: 10.1111/j.1349-7006.2008.01053.x 19154413.
48. Standard J, Jiang Y, Yu M, Su X, Zhao Z, Xu J, et al. Reduced signaling of PI3K-Akt and RAS-MAPK pathways is the key target for weight-loss-induced cancer prevention by dietary calorie restriction and/or physical activity. The Journal of nutritional biochemistry. 2014;25(12):1317–23. Epub 2014/10/07. doi: 10.1016/j.jnutbio.2014.07.010 25283328
49. Sakamoto K, Aschenbach WG, Hirshman MF, Goodyear LJ. Akt signaling in skeletal muscle: regulation by exercise and passive stretch. American journal of physiology-Endocrinology and metabolism. 2003;285(5):E1081–E8. doi: 10.1152/ajpendo.00228.2003 12837666
50. Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y, et al. IL-1 is required for tumor invasiveness and angiogenesis. Proceedings of the National Academy of Sciences. 2003;100(5):2645–50.
51. Steeve KT, Marc P, Sandrine T, Dominique H, Yannick F. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine & growth factor reviews. 2004;15(1):49–60.
52. Fong Y, Moldawer LL, Marano M, Wei H, Barber A, Manogue K, et al. Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 1989;256(3):R659–R65.
53. Jagielska B, Poniatowska G, Tałasiewicz K, Demkow T, Wiechno P. Systemic complications in the hormonal treatment of prostate and breast cancer. Nowotwory Journal of Oncology. 2017;67(3):206–14.
54. Lee YM, Fujikado N, Manaka H, Yasuda H, Iwakura Y. IL-1 plays an important role in the bone metabolism under physiological conditions. International immunology. 2010;22(10):805–16. Epub 2010/08/04. doi: 10.1093/intimm/dxq431 20679512.
55. Winters-Stone KM, Dobek JC, Bennett JA, Maddalozzo GF, Ryan CW, Beer TM. Skeletal Response to Resistance and Impact Training in Prostate Cancer Survivors. Medicine and science in sports and exercise. 2014;46(8):1482–8. doi: 10.1249/MSS.0000000000000265 24500540
56. Agarwal M, He C, Siddiqui J, Wei JT, Macoska JA. CCL11 (eotaxin-1): A new diagnostic serum marker for prostate cancer. The Prostate. 2013;73(6):573–81. doi: 10.1002/pros.22597 23059958
57. Zhu F, Liu P, Li J, Zhang Y. Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3-ERK pathway and upregulation of MMP-3 expression. Oncology reports. 2014;31(5):2049–54. doi: 10.3892/or.2014.3060 24604010
58. Salcedo R, Young HA, Ponce ML, Ward JM, Kleinman HK, Murphy WJ, et al. Eotaxin (CCL11) induces in vivo angiogenic responses by human CCR3+ endothelial cells. The Journal of Immunology. 2001;166(12):7571–8. doi: 10.4049/jimmunol.166.12.7571 11390513
59. Dewhirst MW, Cao Y, Moeller B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nature Reviews Cancer. 2008;8(6):425. doi: 10.1038/nrc2397 18500244
60. Jain RK. Determinants of tumor blood flow: a review. Cancer research. 1988;48(10):2641–58. Epub 1988/05/15. 3282647.
61. Ma J, Waxman DJ. Combination of antiangiogenesis with chemotherapy for more effective cancer treatment. Molecular cancer therapeutics. 2008;7(12):3670–84. Epub 2008/12/17. doi: 10.1158/1535-7163.MCT-08-0715 19074844
62. Perrot-Applanat M, Di Benedetto M. Autocrine functions of VEGF in breast tumor cells: Adhesion, survival, migration and invasion. Cell Adhesion & Migration. 2012;6(6):547–53. doi: 10.4161/cam.23332 23257828
63. Breuss JM, Uhrin P. VEGF-initiated angiogenesis and the uPA/uPAR system. Cell Adhesion & Migration. 2012;6(6):535–40. doi: 10.4161/cam.22243 23076133
64. Goel HL, Mercurio AM. Enhancing integrin function by VEGF/neuropilin signaling: Implications for tumor biology. Cell Adhesion & Migration. 2012;6(6):554–60. doi: 10.4161/cam.22419 23076131
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