본문 바로가기
KERD
논문KCI 등재

6-sialyllactose ameliorates dihydrotestosterone-induced benign prostatic hyperplasia through suppressing VEGF-mediated angiogenesis

1

조회

0

다운로드

4

인용

0

참고문헌

키워드

주제분류화학

초록

Benign prostatic hyperplasia (BPH), a common disease in elderly males, is accompanied by non-malignant growth of prostate tissues, subsequently causing hypoxia and angiogenesis. Although VEGF-related angiogenesis is one of the therapeutic targets of prostate cancer, there is no previous study targeting angiogenesis for treatment of BPH. Dihydrotestosterone (DHT)- induced expressions of vascular endothelial growth factor (VEGF) in prostate epithelial RWPE-1 cells and human umbilical vascular endothelial cells (HUVECs). Conditioned media (CM) from DHT-treated RWPE-1 cells were transferred to HUVECs. Then, 6SL inhibited proliferation, VEGFR-2 activation, and tube formation of HUVECs transferred with CM from DHT-treated RWPE-1 cells. In the rat BPH model, 6SL reduced prostate weight, size, and thickness of the prostate tissue. Formation of vessels in prostatic tissues were also reduced with 6SL treatment. We found that 6SL has an ameliorative effect on in vitro and in vivo the BPH model via inhibition of VEGFR-2 activation and subsequent angiogenesis. These results suggest that 6SL might be a candidate for development of novel BPH drugs.

Abstract

Benign prostatic hyperplasia (BPH), a common disease in elderly males, is accompanied by non-malignant growth of prostate tissues, subsequently causing hypoxia and angiogenesis. Although VEGF-related angiogenesis is one of the therapeutic targets of prostate cancer, there is no previous study targeting angiogenesis for treatment of BPH. Dihydrotestosterone (DHT)- induced expressions of vascular endothelial growth factor (VEGF) in prostate epithelial RWPE-1 cells and human umbilical vascular endothelial cells (HUVECs). Conditioned media (CM) from DHT-treated RWPE-1 cells were transferred to HUVECs. Then, 6SL inhibited proliferation, VEGFR-2 activation, and tube formation of HUVECs transferred with CM from DHT-treated RWPE-1 cells. In the rat BPH model, 6SL reduced prostate weight, size, and thickness of the prostate tissue. Formation of vessels in prostatic tissues were also reduced with 6SL treatment. We found that 6SL has an ameliorative effect on in vitro and in vivo the BPH model via inhibition of VEGFR-2 activation and subsequent angiogenesis. These results suggest that 6SL might be a candidate for development of novel BPH drugs.

참고문헌 (41)

  1. Emberton M, "Benign prostatic hyperplasia : a progressive disease of aging men", Urology, 61, pp.267~273 (2003)
  2. O'Leary MP, "Lower urinary tract symptoms", benign prostatic hyperplasia : maintaining symptom control and reducing complications, 2003, pp.62, 15~23
  3. Keledjian K, "Reduction of human prostate tumor vascularity by the alpha1-adrenoceptor antagonist terazosin", Prostate, 48, pp.71~78 (2001)
  4. Carson C 3rd, "The role of dihydrotestosterone in benign prostatic hyperplasia", Urology, 61, pp.2~7 (2003)
  5. Zaman Huri H, "Drug-related problems in patients with benign prostatic hyperplasia : a cross sectional retrospective study", PLoS One, 9, pp.e86215~ (2014)
  6. DuBeau CE, "Controversies in the diagnosis and management of benign prostatic hypertrophy", Adv Intern Med, 37, pp.55~83 (1992)
  7. 정경진, "Expected Next-Generation Drugs Under Development in Relation to Voiding Symptoms", International Neurourology Journal, 21(2), pp.97~101 (2017), 대한배뇨장애요실금학회
  8. McNeal JE, "Origin and evolution of benign prostatic enlargement", Invest Urol, 15, pp.340~345 (1978)
  9. Lekas A, "The expression of hypoxia-inducible factor-1alpha(HIF-1alpha)and angiogenesis markers in hyperplastic and malignant prostate tissue", Anticancer Res, 26, pp.2989~2993 (2006)
  10. Wu F, "Elevated expression of HIF-lalpha in actively growing prostate tissues is associated with clinical features of benign prostatic hyperplasia", Oncotarget, 7, pp.12053~12062 (2016)
  11. Pareek G, "The effect of finasteride on the expression of vascular endothelial growth factor and microvessel density : a possible mechanism for decreased prostatic bleeding in treated patients", J Urol, 169, pp.20~23 (2003)
  12. Stefanou D, "Expression of vascular endothelial growth factor(VEGF)and association with microvessel density in benign prostatic hyperplasia and prostate cancer", In Vivo, 18, pp.155~160 (2004)
  13. Aweimer A, "Regulation of soluble VEGFR-2 secreted by microvascular endothelial cells derived from human BPH", Prostate Cancer Prostatic Dis, 15, pp.157~164 (2012)
  14. Berger AP, "Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia", Prostate, 57, pp.57~65 (2003)
  15. Jackson MW, "Vascular endothelial growth factor(VEGF)expression in prostate cancer and benign prostatic hyperplasia", J Urol, 157, pp.2323~2328 (1997)
  16. Lekas AG, "Finasteride effects on hypoxia and angiogenetic markers in benign prostatic hyperplasia", Urology, 68, pp.436~441 (2006)
  17. Sordello S, "Vascular endothelial growth factor is up-regulated in vitro and in vivo by androgens", Biochem Biophys Res Commun, 251, pp.287~290 (1998)
  18. Levine AC, "Androgens induce the expression of vascular endothelial growth factor in human fetal prostatic fibroblasts", Endocrinology, 139, pp.4672~4678 (1998)
  19. Foo KT, "Pathophysiology of clinical benign prostatic hyperplasia", Asian J Urol, 4, pp.152~157 (2017)
  20. Wen J, "Suppression of DHT-induced paracrine stimulation of endothelial cell growth by estrogens via prostate cancer cells", Prostate, 73, pp.1069~1081 (2013)
  21. Wu S, "Annotation and structural analysis of sialylated human milk oligosaccharides", J Proteome Res, 10, pp.856~868 (2011)
  22. Yonekawa T, "Sialyllactose ameliorates myopathic phenotypes in symptomatic GNE myopathy model mice", Brain, 137, pp.2670~2679 (2014)
  23. Bode L, "Human milk oligosaccharides : every baby needs a sugar mama", Glycobiology, 22, pp.1147~1162 (2012)
  24. Chung TW, "Sialyllactose suppresses angiogenesis by inhibiting VEGFR-2 activation, and tumor progression", Oncotarget, 8, pp.58152~58162 (2017)
  25. Vaarala MH, "Identification of androgen-regulated genes in human prostate", Mol Med Rep, 6, pp.466~472 (2012)
  26. 박성아, "Structure and function of vascular endothelial growth factor and its receptor system", BMB Reports, 51(2), pp.73~78 (2018), 생화학분자생물학회
  27. Li J, "Testosterone-induced benign prostatic hyperplasia rat and dog as facile models to assess drugs targeting lower urinary tract symptoms", PLoS One, 13, pp.e0191469~ (2018)
  28. Kim SK, "Inhibitory effect of curcumin on testosterone induced benign prostatic hyperplasia rat model", BMC Complement Altern Med, 15, pp.380~ (2015)
  29. Minutoli L, "Serenoa repens, lycopene and selenium : a triple therapeutic approach to manage benign prostatic hyperplasia", Curr Med Chem, 20, pp.1306~1312 (2013)
  30. Said MM, "Flaxseed suppressed prostatic epithelial proliferation in a rat model of benign prostatic hyperplasia", J Toxicol Environ Health A, 78, pp.453~465 (2015)
  31. Kim JH, "Efficacy and safety of 5 alpha-reductase inhibitor monotherapy in patients with benign prostatic hyperplasia : A meta-analysis", PLoS One, 13, pp.e0203479~ (2018)
  32. Jun JEJ, "5alpha-Reductase inhibitors for treatment of benign prostatic hyperplasia : A systematic review and metaanalysis", Can J Hosp Pharm, 70, pp.113~119 (2017)
  33. Thomas D, "Emerging drugs for the treatment of benign prostatic hyperplasia", Expert Opin Emerg Drugs, 22, pp.201~212 (2017)
  34. Bostwick DG, "Microvessel density in prostate cancer : prognostic and therapeutic utility", Semin Urol Oncol, 16, pp.118~123 (1998)
  35. Padhani AR, "Angiogenesis imaging in the management of prostate cancer", Nat Clin Pract Urol, 2, pp.596~607 (2005)
  36. Ravindranath N, "Epidermal growth factor modulates the expression of vascular endothelial growth factor in the human prostate", J Androl, 22, pp.432~443 (2001)
  37. ten Bruggencate SJ, "Functional role and mechanisms of sialyllactose and other sialylated milk oligosaccharides", Nutr Rev, 72, pp.377~389 (2014)
  38. Godoy A, "Androgen deprivation induces rapid involution and recovery of human prostate vasculature", Am J Physiol Endocrinol Metab, 300, pp.E263~275 (2011)
  39. Chung HK, "Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis", J Cell Biol, 216, pp.149~165 (2017)
  40. Ryu D, "A SIRT7-dependent acetylation switch of GABPbeta1 controls mitochondrial function", Cell Metab, 20, pp.856~869 (2014)
  41. Chung TW, "CAPE suppresses VEGFR-2 activation, and tumor neovascularization and growth", J Mol Med(Berl), 91, pp.271~282 (2013)

관련 논문AI추천

Effects of Oxya chinensis sinuosa hot water extract on benign prostatic hyperplasia in LNCaP cells권해용, 김인우, 박소현, 서민철, 이준하, 최라영, Hyun Jung Lim한국잠사학회 · International Journal of Industrial Entomology and Biomaterials2023 · 제47권 제2호Ameliorative effect of Abeliophyllum distichum Nakai on benign prostatic hyperplasia in vitro and in vivo김은경, 이상무, Bae Sung Mun, Choi Young-Jin, Fan Meiqi, Lee Bokyung, Lee Seung-Hyun, Moon Sangho, Tang Yujiao한국영양학회 · Nutrition Research and Practice2022 · 제16권 제4호Heat-Killed and Live Enterococcus faecalis Attenuates Enlarged Prostate in an Animal Model of Benign Prostatic Hyperplasia김은경, 이보경, 이홍찬, 최영진, 황지영, Fan Meiqi, Han Kwon-Il, Iwasa Masahiro, Tang Yujiao한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2021 · 제31권 제8호The combination of water extracts of Curcumae Radix and Syzygii Flos improves benign prostatic hyperplasia by suppressing testosterone-induced proliferation of prostate cells in vivo and in vitro곽현정, 박자연, Beomsu Lee, Gahee Song, Jae-Young Um, Jinbong Park, Kwang Seok Ahn, Woo Yong Park, Yunu Jung한국영양학회 · Nutrition Research and Practice2025 · 제19권 제3호Asparagi radix alleviates testosterone-induced benign prostatic hyperplasia by inhibiting 5α-reductase activity and androgen receptor signaling pathway김기영, 김다혜, 노정숙, 문성권, 최영현, Hee-Jae Cha, Heui-Soo Kim, Hyun HwangBo, Ji Seon Yeong, Kim Min Yeong, Tae Hee Kim한국영양학회 · Nutrition Research and Practice2024 · 제18권 제6호Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats박철, 권다혜, 김경일, 김기영, 김민영, 김범회, 김종식, 박노진, 안규임, 정지숙, 지선영, 최영현, 최은옥, 홍수현, 황보현한국영양학회 · Nutrition Research and Practice2018 · 제12권 제5호

이 간행물의 다른 논문 (6건)