JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.2 P.161-171

Effects of astaxanthin on oxidative stress induced by Cu²⁺ in prostate cells

Author(s): Hong-zhou Meng, Xiao-feng Ni, Hai-ning Yu, Shan-shan Wang, Sheng-rong Shen
Affiliation(s): Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more
Corresponding email(s): shrshen@zju.edu.cn
Key Words: Oxidative stress, PC-3, RWPE-1, Astaxanthin, Copper ion

Share this article to： More <<< Previous Article \|Next Article >>>

Abstract: astaxanthin (AST), a carotenoid molecule extensively found in marine organisms and increasingly used as a dietary supplement, has been reported to have beneficial effects against oxidative stress. In the current paper, the effects of AST on viability of prostate cells were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay; cell apoptosis and intracellular reactive oxygen species (ROS) levels were determined by flow cytometry; the mitochondrial membrane potential (MMP) was measured by fluorospectrophotometer; and activities of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were evaluated by a detection kit. The results show that copper ion (Cu²⁺) induced apoptosis, along with the accumulation of intracellular ROS and MDA, in both prostate cell lines (RWPE-1 and PC-3). AST treatments could decrease the MDA levels, increase MMP, and keep ROS stable in RWPE-1 cell line. An addition of AST decreased the SOD, GSH-Px, and CAT activities in PC-3 cell line treated with Cu²⁺, but had a contrary reaction in RWPE-1 cell lines. In conclusion, AST could contribute to protecting RWPE-1 cells against Cu²⁺-induced injuries but could cause damage to the antioxidant enzyme system in PC-3 cells.

虾青素对铜离子诱导的前列腺细胞氧化损伤的影响

目的：研究虾青素对铜离子诱导的前列腺细胞氧化损伤的影响，并探索其作用机制。
创新点：首次研究虾青素对铜离子诱导的前列腺细胞及前列腺癌细胞氧化损伤的影响，并比较其对两种细胞作用的差异。
方法：MTT法测定铜离子与虾青素对前列腺细胞（RWPE-1）和前列腺癌细胞（PC-3）生长的影响；采用细胞流式仪测定虾青素对铜离子诱导的RWPE-1和PC-3细胞凋亡的影响；荧光分光光度法测定了虾青素对铜离子诱导的活性氧自由基（ROS）产生的影响；采用罗丹明123（Rh123）染色检测虾青素对铜离子诱导的细胞线粒体膜电位（MMP）变化的影响；采用试剂盒测定了虾青素对铜离子存在下丙二醛（MDA）含量、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）及谷胱甘肽过氧化物酶（GSH-Px）活性变化的影响。
结论：结果表明，铜离子能诱导RWPE-1和PC-3细胞凋亡，并伴随细胞内ROS和MDA含量升高；虾青素处理可显著降低RWPE-1细胞中MDA含量，升高线粒体膜电位，并保持ROS含量稳定；虾青素处理可降低PC-3细胞中SOD、GSH-Px和CAT的活性，而对RWPE-1细胞则作用相反。因此，虾青素处理能有效降低铜离子对RWPE-1细胞引起的损伤，而通过降低抗氧化酶活性加剧铜离子对PC-3细胞的损伤。

关键词：氧化损伤；PC-3细胞；RWPE-1细胞；虾青素；铜离子

Reference

[1]Adler, V., Yin, Z., Tew, K.D., et al., 1999. Role of redox potential and reactive oxygen species in stress signaling. Oncogene, 18(45):6104-6111.

[2]Ambati, R.R., Phang, S.M., Ravi, S., et al., 2014. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications—a review. Mar. Drugs, 12(1):128-152.

[3]Auten, R.L., Davis, J.M., 2009. Oxygen toxicity and reactive oxygen species: the devil is in the details. Pediatr. Res., 66(2):121-127.

[4]Banci, L., Bertini, I., Cantini, F., et al., 2010. Cellular copper distribution: a mechanistic systems biology approach. Cell. Mol. Life Sci., 67(15):2563-2589.

[5]Barros, M.P., Poppe, S.C., Bondan, E.F., 2014. Neuroprotective properties of the marine carotenoid astaxanthin and omega-3 fatty acids, and perspectives for the natural combination of both in krill oil. Nutrients, 6(3):1293-1317.

[6]Basu, H.S., Thompson, T.A., Church, D.R., et al., 2009. A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model. Cancer Res., 69(19):7689-7695.

[7]Brawek, B., Lӧffler, M., Wagner, K., et al., 2010. Reactive oxygen species (ROS) in the human neocortex: role of aging and cognition. Brain Res. Bull., 81(4-5):484-490.

[8]de Feo, C.J., Aller, S.G., Siluvai, G.S., et al., 2009. Three-dimensional structure of the human copper transporter hCTR1. PNAS, 106(11):4237-4242.

[9]de Haan, J.B., Cristiano, F., Iannello, R., et al., 1996. Elevation in the ratio of Cu/Zn-superoxide dismutase to glutathione peroxidase activity induces features of cellular senescence and this effect is mediated by hydrogen peroxide. Hum. Mol. Genet., 5(2):283-292.

[10]Dröge, W., 2002. Free radicals in the physiological control of cell function. Physiol. Rev., 82(1):47-95.

[11]Fassett, R.G., Coombes, J.S., 2009. Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol., 5(4):333-342.

[12]Festa, R.A., Thiele, D.J., 2011. Copper: an essential metal in biology. Curr. Biol., 21(21):R877-R883.

[13]Frohlich, D.A., McCabe, M.T., Arnold, R.S., et al., 2008. The role of Nrf2 in increased reactive oxygen species and DNA damage in prostate tumorigenesis. Oncogene, 27(31):4353-4362.

[14]Haas, K.L., Putterman, A.B., White, D.R., et al., 2011. Model peptides provide new insights into the role of histidine residues as potential ligands in human cellular copper acquisition via Ctr1. J. Am. Chem. Soc., 133(12):4427-4437.

[15]Kim, B.E., Nevitt, T., Thiele, D.J., 2008. Mechanisms for copper acquisition, distribution and regulation. Nat. Chem. Biol., 4(3):176-185.

[16]Kimura, M., Iida, M., Yamauchi, H., et al., 2014. Astaxanthin supplementation effects on adipocyte size and lipid profile in OLETF rats with hyperphagia and visceral fat accumulation. J. Funct. Foods, 11:114-120.

[17]Kuroki, M., Voest, E.E., Amano, S., et al., 1996. Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo. J. Clin. Invest., 98(7):1667.

[18]Linder, M.C., 2012. The relationship of copper to DNA damage and damage prevention in humans. Mutat. Res., 733(1-2):83-91.

[19]Liu, X., Osawa, T., 2009. Astaxanthin protects neuronal cells against oxidative damage and is a potent candidate for brain food. In: Yoshikawa, T. (Ed.), Food Factors for Health Promotion. Forum of Nutrition, Karger, Basel, Vol. 61, p.129-135.

[20]Ma, L., Li, X., Wang, Y., et al., 2014. Cu(II) inhibits hIAPP fibrillation and promotes hIAPP-induced beta cell apoptosis through induction of ROS-mediated mitochondrial dysfunction. J. Inorg. Biochem., 140:143-152.

[21]Maltepe, E., Saugstad, O.D., 2009. Oxygen in health and disease: regulation of oxygen homeostasis-clinical implications. Pediatr. Res., 65(3):261-268.

[22]Mira, L., Tereza Fernandez, M., Santos, M., et al., 2002. Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity. Free Radic. Res., 36(11):1199-1208.

[23]Montezano, A.C., Touyz, R.M., 2012. Molecular mechanisms of hypertension—reactive oxygen species and antioxidants: a basic science update for the clinician. Can. J. Cardiol., 28(3):288-295.

[24]Murphy, A., Taiz, L., 1997. Correlation between potassium efflux and copper sensitivity in 10 Arahidopsis ecotypes. New Phytol., 136(2):211-222.

[25]Ohgami, K., Shiratori, K., Kotake, S., et al., 2003. Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Invest. Ophthalmol. Vis. Sci., 44(6):2694-2701.

[26]Paschos, A., Pandya, R., Duivenvoorden, W.C.M., et al., 2013. Oxidative stress in prostate cancer: changing research concepts towards a novel paradigm for prevention and therapeutics. Prostate Cancer Prostatic Dis., 16(3):217-225.

[27]Pashkow, F.J., Watumull, D.G., Campbell, C.L., 2008. Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am. J. Cardiol., 101(10):S58-S68.

[28]Preuss, H.G., Echard, B., Bagchi, D., et al., 2009. Astaxanthin lowers blood pressure and lessens the activity of the renin-angiotensin system in Zucker Fatty Rats. J. Funct. Foods, 1(1):13-22.

[29]Rajeshkumar, R.K., Vennila, R., Karthikeyan, S., et al., 2015. Antiproliferative activity of marine stingray Dasyatis sephen venom on human cervical carcinoma cell line. J. Venomous Anim. Toxins Incl. Trop. Dis., 21:41.

[30]Ripple, M.O., Wilding, G., Henry, W.F., et al., 1997. Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells. J. Natl. Cancer Inst., 89(1):40-48.

[31]Rodríguez-Sureda, V., Vilches, Á., Sánchez, O., et al., 2015. Intracellular oxidant activity, antioxidant enzyme defense system, and cell senescence in fibroblasts with trisomy 21. Oxid. Med. Cell. Longev., 2015:509241.

[32]Rosenzweig, A.C., O'Halloran, T.V., 2000. Structure and chemistry of the copper chaperone proteins. Curr. Opin. Chem. Biol., 4(2):140-147.

[33]Saha, N.R., Usami, T., Suzuki, Y., 2003. A double staining flow cytometric assay for the detection of steroid induced apoptotic leucocytes in common carp (Cyprinus carpio). Dev. Comp. Immunol., 27(5):351-363.

[34]Schewe, T., 2002. 15-Lipoxygenase-1: a prooxidant enzyme. Biol. Chem., 383(3-4):365-374.

[35]Shen, Y.Z., 2014. Biological behaviors of prostate cells with PUFAs supplementation. MS Thesis, Zhejiang University, Hangzhou, China (in Chinese).

[36]Sies, H., 1985. Oxidative stress: introductory remarks. In: Sies, H. (Ed.), Oxidative Stress. Academic Press, London, p.1-8.

[37]Sun, X.Y., Donald, S.P., Phang, J.M., 2001. Testosterone and prostate specific antigen stimulate generation of reactive oxygen species in prostate cancer cells. Carcinogenesis, 22(11):1775-1780.

[38]Tam, N.N.C., Gao, Y., Leung, Y.K., et al., 2003. Androgenic regulation of oxidative stress in the rat prostate: involvement of NAD(P)H oxidases and antioxidant defense machinery during prostatic involution and regrowth. Am. J. Pathol., 163(6):2513-2522.

[39]Wang, J.Y., Lee, Y.J., Chou, M.C., et al., 2015. Astaxanthin protects steroidogenesis from hydrogen peroxide-induced oxidative stress in mouse Leydig cells. Mar. Drugs, 13(3):1375-1388.

[40]Winterbourn, C.C., 2008. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol., 4(5):278-286.

[41]Yang, D.J., Lin, J.T., Chen, Y.C., et al., 2013. Suppressive effect of carotenoid extract of Dunaliella salina alga on production of LPS-stimulated pro-inflammatory mediators in RAW264. 7 cells via NF-κB and JNK inactivation. J. Funct. Foods, 5(2):607-615.

[42]Zhang, Y., Wang, W., Hao, C., et al., 2015. Astaxanthin protects PC12 cells from glutamate-induced neurotoxicity through multiple signaling pathways. J. Funct. Foods, 16:137-151.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Similar articles

- Go to

虾青素对铜离子诱导的前列腺细胞氧化损伤的影响

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference