اثرات نانوکامپوزیت گرافن اکسید کوت شده با ۸-هیدروکسی کینولین بر روی مرگ سلولی و آپوپتوز در رده های سلولی سرطان پستان(MCF-7) و سرطان کولون(SW742)
محورهای موضوعی : مجله پلاسما و نشانگرهای زیستیفیروزه خیل تاش 1 , کاظم پریور 2 , نسیم حیاتی رودباری 3 , علیرضا بدیعی 4 , بهنام صادقی 5
1 - گروه زیست شناسی، دانشکده علوم، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران
2 - گروه زیست شناسی، دانشکده علوم، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران
3 - گروه زیست شناسی، دانشکده علوم، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران
4 - گروه شیمی، دانشکده علوم، دانشگاه تهران، تهران، ایران.
5 - گروه ایمنی درمانی سرطان و پزشکی بازساختی، مرکز تحقیقات سرطان پستان، پژوهشکده معتمد، جهاد دانشگاهی، تهران، ایران.
کلید واژه: سرطان پستان, آپوپتوز, گرافن اکسید, سرطان کولون, ۸-هیدروکسی کینولین,
چکیده مقاله :
زمینه و هدف: سرطان پستان در زنان و سرطان کولورکتال در هر دو جنس جزو شایع ترین و کشنده ترین سرطان ها در سراسر جهان می باشند.با توجه به مقاوم بودن برخی از سرطان ها به درمان های رایج، در این تحقیق اثرات سمیت و القائ آپوپتوز نانوکامپوزیت گرافن اکساید کوت شده با ۸-هیدروکسی کینولین بر روی سلول های رده سرطان پستان و کولون سنجیده شد. روش کار: در این مطالعهرده سلولی سرطان پستان(MCF-7)، سرطان کولون(SW-742) و رده سلول نرمال پستان(MCF-10) را با دوزهای مختلف نانوصفحات گرافن اکساید کوت شده با ۸-هیدروکسی کینولینبه مدت ۱۲، ۲۴ و ۴۸ ساعت تیمار و سمیت این نانوکامپوزیت را با روش MTT و تاثیر ماده فوق الذکر در آپوپتوز سلولی هم از طریق بررسی بیان ژن های پیش برنده و مهار کننده آپوپتوز از جمله P53, P21, Bax و Bcl-2 نیز از طریق تست فلوسایتومتری آپوپتوز سلولی(Annexin-V/PI) صورت گرفته شد. یافته ها: نتایج نشان دادند که نانوکامپوزیت سبب افزایش معنادار مرگ سلولی در رده های سلولی سرطان کولون و پستان به خصوص رده MCF-7 در مقایسه با رده سلول نرمال پستان گردیده است. نتایج بیان ژن نیز حاکی از افزایش بیان ژن های پیش آپوپتوزی P53, p21 و Bax و کاهش بیان ژن ضد آپوپتوزی Bcl-2 در رده های سلول سرطانی به خصوص رده MCF-7 به نسبت رده سلول نرمال پستان است. نتایج فلوسایتومتری تست Annexin-V/PI نیز در همین راستا القائ آپوپتوز در رده های سرطانی بالاخص MCF-7 به نسبت نمونه کنترل را پس از تیمار با نانوکامپوزیت نشان داد. نتیجه گیری: یکی از مکانیسم های القائ مرگ سلولی استفاده از نانوکامپوزیت با القائ آپوپتوز در آن ها می باشد.
1. Afzal, O., Kumar, S., Haider, MR., Ali, MR., Kumar, R., Jaggi, M. (2015). A review on anticancer potential of bioactive heterocycle quinoline. European Journal of Medicinal Chemistry, 97; 871-910.
2.Ai, Y., Liang, Y-J., Liu, J-C., He, H-W., Chen, Y., Tang, C. (2012). Synthesis and in vitro antiproliferative evaluation of pyrimido [5, 4-c] quinoline-4-(3H)-one derivatives. European Journal Of Medicinal Chemistry, 47;206-13.
3.Alibolandi, M., Mohammadi, M., Taghdisi, SM., Ramezani, M., Abnous, K. (2017). Fabrication of aptamer decorated dextran coated nano-graphene oxide for targeted drug delivery. Carbohydrate Polymers, 155; 218-29.
4.Badiei, A., Goldooz, H., Ziarani, GM. (2011). A novel method for preparation of 8-hydroxyquinoline functionalized mesoporous silica: Aluminum complexes and photoluminescence studies. Applied Surface Science, 257(11); 4912-8.
5.Barilli, A., Atzeri, C., Bassanetti, I., Ingoglia, F., Dall’Asta, V., Bussolati, O. (2014). Oxidative stress induced by copper and iron complexes with 8-hydroxyquinoline derivatives causes paraptotic death of HeLa cancer cells. Molecular Pharmaceutics, 11(4); 1151-63.
6.Bhushan, B. (2017). Springer handbook of nanotechnology: Springer.
7.Bianco, A. (1997).Graphene: safe or toxic? The two faces of the medal. Angewandte Chemie International Edition, 19;52-97.
8.Bray, F., Ferlay, J., Soerjomataram, I., Siegel, RL., Torre, LA., Jemal, A. (2018). Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians, 68(6);424-394.
9.Bressan, E., Ferroni, L., Gardin, C., Sbricoli, L., Gobbato, L., (2014). Graphene based scaffolds effects on stem cells commitment. Journal of Translational Medicine, 12(1); 296.
10.Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. (1998). Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science, 282(5393); 1497-501.
11.Canel, C., Moraes, R., Dayan, F., Ferreira, D. (2000). Molecules of interest: podophyllotoxin, Phytochem, 54: 115-120.
12.Chan, SH., Chui, CH., Chan, SW., Kok, SHL., Chan, D.(2012). Synthesis of 8-hydroxyquinoline derivatives as novel antitumor agents. ACS Medicinal Chemistry Letters, 4(2);170-4.
13.Chandler, D., El-Naggar, AK., Brisbay, S., Redline, RW., McDonnell, TJ. (1994). Apoptosis and expression of the bcl-2 proto-oncogene in the fetal and adult human kidney: evidence for the contribution of bcl-2 expression to renal carcinogenesis. Human Pathology, 25(8); 789-96.
14.Chang, Y., Yang, S-T., Liu, J-H., Dong, E., Wang, Y., Cao, A. (2011). In vitro toxicity evaluation of graphene oxide on A549 cells. Toxicology Letters, 200(3);201-10.
15.Chen, C., Hou, X., Wang, G., Pan, W., Yang, X., Zhang, Y. (2017). Design, synthesis and biological evaluation of quinoline derivatives as HDAC class I inhibitors. European Journal of Medicinal Chemistry, 133; 11-23.
16.Chen, L., Hu, P., Zhang, L., Huang, S., Luo, L., Huang, C. (2012). Toxicity of graphene oxide and multi-walled carbon nanotubes against human cells and zebrafish. Science China Chemistry, 55(10);22.
17.Chowdhury, SM., Lalwani, G., Zhang, K., Yang, JY., Neville, K., Sitharaman, B. (2013). Cell specific cytotoxicity and uptake of graphene nanoribbons. Biomaterials, 34(1); 283-93.
18.Chua, CK., Pumera, M. (2014). Chemical reduction of graphene oxide: a synthetic chemistry viewpoint. Chemical Society Reviews, 43(1); 291-312.
19.Dakubo, GD. (2010). Mitochondrial genetics and cancer: Springer Science & Business Media, 20-10.
20.Deb, A., Vimala, R. (2018). Camptothec in loaded graphene oxide nanoparticle functionalized with polyethylene glycol and folic acid for anticancer drug delivery. Journal of Drug Delivery Science and Technology, 43; 333-42.
21.Ding, W-Q., Liu, B., Vaught, JL., Yamauchi, H., Lind, SE. (2005). Anticancer activity of the antibiotic clioquinol. Cancer Research, 65(8); 3389-95.
22.Ding, WQ., Lind, SE. (2009). Metal ionophores–an emerging class of anticancer drugs. IUBMB Life, 61(11); 1013-8.
23.Dreaden, EC., Alkilany, AM., Huang, X., Murphy, CJ., El-Sayed, MA. (2012). The golden age: gold nanoparticles for biomedicine. Chemical Society Reviews,79;27-40.
24.Du, W. (2003). Towards new anticancer drugs: a decade of advances in synthesis of camptothecins and related alkaloids. Tetrahedron, 59(44); 8649-87.
25.Du, W., Jiang, X., Zhu, L. (2013). From graphite to graphene: direct liquid-phase exfoliation of graphite to produce single-and few-layered pristine graphene. Journal of Materials Chemistry A, 1(36); 10592-606.
26.El-Deiry, WS., Tokino, T., Velculescu, VE., Levy, DB., Parsons, R., Trent, JM. (1998). WAF1, a potential mediator of p53 tumor suppression. Cell, 3(4);25-17.
27.Fan, L., Ge, H., Zou, S., Xiao, Y., Wen, H., Li, Y. (2016). Sodium alginate conjugated graphene oxide as a new carrier for drug delivery system. International Journal of Biological Macromolecules, 93; 582-90.
28.Fiorillo, M., Verre, AF., Iliut, M., Peiris-Pagés, M., Ozsvari, B., Gandara, R. (2015). Graphene oxide selectively targets cancer stem cells, across multiple tumor types: implications for non-toxic cancer treatment, via “differentiation-based nano-therapy”. Oncotarget, 6(6); 3553.
29.Fulda, S., Debatin, K-M. (2006). Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 25(34); 4798.
30.Gupte, A., Mumper, RJ. (2009). Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treatment Reviews,35(1);32-46.
31.Hanahan, D., Weinberg, RA. (2000). The hallmarks of cancer. Cell, 100(1); 57-70.
32.Helsel, ME., Franz, KJ. (2015). Pharmacological activity of metal binding agents that alter copper bioavailability. Dalton Transactions, 44(19); 8760-70.
33.Hou, L., Shi, Y., Jiang, G., Liu, W., Han, H., Feng, Q. (2016). Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery. Nanotechnology, 27(31); 315105.
34.Hummers, Jr WS., Offeman, RE. (1985). Preparation of graphitic oxide. Journal of the American Chemical Society, 80(6); 1339.
35.Hussien, NA., Işıklan, N., Türk, M. (2018). Aptamer-functionalized magnetic graphene oxide nanocarrier for targeted drug delivery of paclitaxel. Materials Chemistry and Physics, 211; 479-88.
36.Jafarizad, A., Aghanejad, A., Sevim, M., Metin, Ö., Barar, J., Omidi, Y. (2017). Gold Nanoparticles and reduced graphene oxide‐gold nanoparticle composite materials as covalent drug delivery systems for breast cancer treatment. Chemistry Select, 2(23); 6663-72.
37.Jiang, H., Taggart, JE., Zhang, X., Benbrook, DM., Lind, SE., Ding, W-Q. (2011). Nitroxoline(8-hydroxy-5-nitroquinoline) is more a potent anti-cancer agent than clioquinol (5-chloro-7-iodo-8-quinoline). Cancer Letters, 312(1); 11-7.
38.Krawczyk, M., Pastuch-Gawolek, G., Mrozek-Wilczkiewicz, A., Kuczak, M., Skonieczna, M., Musiol, R. (2019). Synthesis of 8-hydroxyquinoline glycoconjugates and preliminary assay of their β1, 4-GalT inhibitory and anti-cancer properties. Bioorganic Chemistry, 84; 326-38.
39.Ku, SH., Park, CB. (2013). Myoblast differentiation on graphene oxide. Biomaterials, 34(8); 2017-23.
40.Lei, H., Xie, M., Zhao, Y., Zhang, F., Xu, Y., Xie, J. (2016). Chitosan/sodium alginate modificated graphene oxide-based nanocomposite as a carrier for drug delivery. Ceramics International, 42(15); 1779.
41.Liu, W., Li, X., Wong, Y-S., Zheng, W., Zhang, Y., Cao, W. (2012). Selenium nanoparticles as a carrier of 5-fluorouracil to achieve anticancer synergism. Acs Nano, 6(8); 6578-91.
42.Liu X, Cheng X, Wang F, Feng L, Wang Y, Zheng Y, et al. Targeted delivery of SNX-2112 by polysaccharide-modified graphene oxide nanocomposites for treatment of lung cancer. Carbohydrate Polymers, 185; 85-95.
43.Liu, Y-C., Chen, Z-F., Song, X-Y., Peng, Y., Qin, Q-P., Liang, H. (2013). Synthesis, crystal structure, cytotoxicity and DNA interaction of 5, 7-dibromo-8-quinolinolato-lanthanides. European Journal of Medicinal Chemistry, 59; 168-75.
44.Liu, Y., Zhong, H., Qin, Y., Zhang, Y., Liu, X., Zhang, T. (2016). Non-covalent hydrophilization of reduced graphene oxide used as a paclitaxel vehicle. RSC Advances, 6(36); 30184-93.
45.Liu, Z., Robinson, JT., Sun, X., Dai, H. (2008). Pegylated nanographene oxide for delivery of water-insoluble cancer drugs. Journal of the American Chemical Society, 130(33); 10876-7.
46.Livak, KJ., Schmittgen, TD. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 25(4); 402-8.
47.Luiza, BdO., Borgati, TF., de Freitas, RP., Ruiz, AL., Marchetti, GM., de Carvalho, JE. (2014). Synthesis and antiproliferative activity of 8-hydroxyquinoline derivatives containing a 1, 2, 3-triazole moiety. European Journal of Medicinal Chemistry, 84; 595-604.
48.Lv, Y., Tao, L., Bligh, SA., Yang, H., Pan, Q., Zhu, L. (2016). Targeted delivery and controlled release of doxorubicin into cancer cells using a multifunctional graphene oxide. Materials Science and Engineering: C, 59; 652-60.
49.Masoudipour, E., Kashanian, S., Maleki, N. (2017). A targeted drug delivery system based on dopamine functionalized nano graphene oxide. Chemical Physics Letters, 668; 56-63.
50.Matlack, KE., Tardiff, DF., Narayan, P., Hamamichi, S., Caldwell, KA., Caldwell, GA. (2014). Clioquinol promotes the degradation of metal-dependent amyloid-β (Aβ) oligomers to restore endocytosis and ameliorate Aβ toxicity. Proceedings of the National Academy of Sciences, 201(40); 22-28.
51.Mazur, J., Roy, K., Kanwar, JR. (2018). Recent advances in nanomedicine and survivin targeting in brain cancers. Nanomedicine, 13(1); 105-37.
52.Milacic, V., Jiao, P., Zhang, B., Yan, B., Dou, QP. (2009). Novel 8-hydroxylquinoline analogs induce copper-dependent proteasome inhibition and cell death in human breast cancer cells. International Journal of Oncology, 35(6); 1481-91.
53.Paulchamy, B., Arthi, G., Lignesh, B. (2015). A simple approach to stepwise synthesis of graphene oxide nanomaterial. Journal of Nanomedicine & Nanotechnology, 6(1); 1.
54.Pierson, HO. (2012). Handbook of carbon, graphite, diamonds and fullerenes: processing, properties and applications: William Andrew,
55. Prachayasittikul, V., Prachayasittikul, S., Ruchirawat, S., Prachayasittikul, V. (2013). 8-hydroxy quinolines: a review of their metal chelating properties and medicinal applications. Drug Design, Development and Therapy, 7; 1157.
56.Priyadarsini, RV., Murugan, RS., Maitreyi, S., Ramalingam, K., Karunagaran, D., Nagini, S. (2010). The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer(HeLa) cells through p53 induction and NF-κB inhibition. European Journal of Pharmacology. 649(1-3); 84-91.
57.Qin, Q-P., Chen, Z-F., Qin, J-L., He, X-J., Li, Y-L., Liu, Y-C. (2015). Studies on antitumor mechanism of two planar platinum(II) complexes with 8-hydroxyquinoline: synthesis, characterization, cytotoxicity, cell cycle and apoptosis. European Journal of Medicinal Chemistry, 92; 302-13.
58.Rajpal, S., Venook, A. (2004). Targeted therapy in colorectal cancer. Clinical Advances in Hematology & Oncology: H&O, 4(2); 124-32.
59.Rao, Z., Ge, H., Liu, L., Zhu, C., Min, L., Liu, M. (2018). Carboxymethyl cellulose modified graphene oxide as pH-sensitive drug delivery system. International Journal of Biological Macromolecules, 107; 1184-92.
60.Sahu, A., Choi, WI., Tae, G. (2012). A stimuli-sensitive injectable graphene oxide composite hydrogel. Chemical Communications, 48(47); 5820-2.
61.Sasidharan, A., Panchakarla, L., Chandran, P., Menon, D., Nair, S., Rao, C. (2011). Differential nano-bio interactions and toxicity effects of pristine versus functionalized graphene. Nanoscale, 3(6); 2461-4.
62.Sasidharan, A., Panchakarla, LS., Sadanandan, AR., Ashokan, A., Chandran, P., Girish, CM. (2012). Hemo compatibility and macrophage response of pristine and functionalized graphene. Small, 8(8); 1251-63.
63.Sharma, GN., Dave, R., Sanadya, J., Sharma, P., Sharma, K. (2010). Various types and management of breast cancer: an overview. Journal of Advanced Pharmaceutical Technology & Research, 1; 109-112.
64.Shen, Ay., Wu, Sn., Chiu, Ct. (1999). Synthesis and cytotoxicity evaluation of some 8‐hydroxyquinoline derivatives. Journal of Pharmacy and Pharmacology, 51(5); 543-8.
65.Singh, SK., Singh, MK., Kulkarni, PP., Sonkar, VK., Grácio, JJ., Dash, D. (2012). Amine-modified graphene: thrombo-protective safer alternative to graphene oxide for biomedical applications. ACS Nano, 6(3); 2731-40.
66.Singh, SK., Singh, MK., Nayak, MK., Kumari, S., Shrivastava, S., Grácio, JJ. (2011). Thrombus inducing property of atomically thin graphene oxide sheets. Acs Nano, 5(6); 4987-96.
67.Srivastava, V., Negi, AS., Kumar, J., Gupta, M., Khanuja, SP. (2005). Plant-based anticancer molecules: a chemical and biological profile of some important leads. Bioorganic & Medicinal Chemistry, 13(21); 5892-908.
68.Stewart, BW. (1994). Mechanisms of apoptosis: integration of genetic, biochemical, and cellular indicators. JNCI: Journal of the National Cancer Institute, 86(17); 1286-96.
69.Tan, J., Meng, N., Fan, Y., Su, Y., Zhang, M., Xiao, Y. (2016). Hydroxypropyl-β-cyclodextrin–graphene oxide conjugates: Carriers for anti-cancer drugs. Materials Science and Engineering: C, 61; 681-7.
70.Thapa, RK., Kim, JH., Jeong, J-H., Shin, BS., Choi, H-G., Yong, CS. (2017). Silver nanoparticle-embedded graphene oxide-methotrexate for targeted cancer treatment. Colloids and Surfaces B: Biointerfaces, 153; 95-103.
71.Vajtai, R. (2013). Springer handbook of nanomaterials: Springer Science & Business Media,
72.Wang, C., Xu, H., Liang, C., Liu, Y., Li, Z., Yang, G. (2013). Iron oxide polypyrrole nanoparticles as a multifunctional drug carrier for remotely controlled cancer therapy with synergistic antitumor effect. ACS Nano, 7(8); 6782-95.
73.Wang, N., Świtalska, M., Wu, M-Y., Imai, K., Ngoc, TA., Pang, C-Q. (2014). Synthesis and in vitro cytotoxic effect of 6-amino-substituted 11H-and 11Me-indolo [3, 2-c] quinolines. European Journal of Medicinal Chemistry, 78; 314-23.
74.Wang, Y., Liu, J., Liu, L., Sun, DD. (2011). High-quality reduced graphene oxide-nanocrystalline platinum hybrid materials prepared by simultaneous co-reduction of graphene oxide and chloroplatinic acid. Nanoscale Research Letters, 6(1); 241.
75.Wei, G., Dong, R., Wang, D., Feng, L., Dong, S., Song, A. (2014). Functional materials from the covalent modification of reduced graphene oxide and β-cyclodextrin as a drug delivery carrier. New Journal of Chemistry. 38(1); 140-5.
76.Wei, J., Vo, T., Inam, F. (2015). Epoxy/graphene nanocomposites–processing and properties: a review. RSC Advances, 5(90); 73510-24.
77.Wolf, EL. (2014). Applications of graphene: an overview: Springer,
78.Xiao, Z., Lei, F., Chen, X., Wang, X., Cao, L., Ye, K, Design, synthesis, and antitumor evaluation of quinoline‐imidazole derivatives. Archiv der Pharmazie, 351(6); 1700407.
79.Xu, H., Chen, W., Zhan, P., Liu, X. (2015). 8-Hydroxyquinoline: a privileged structure with a broad-ranging pharmacological potential. MedChemComm, 6(1); 61-74.
80.Yadav, N., Kumar, N., Prasad, P., Shirbhate, S., Sehrawat, S., Lochab, B. (2018). Stable dispersions of covalently tethered polymer improved graphene oxide nanoconjugates as an effective vector for siRNA delivery. ACS Applied Materials & Interfaces, 10(17); 14577-93.
81.Yang, D., Li, T., Xu, M., Gao, F., Yang, J., Yang, Z. (2014). Graphene oxide promotes the differentiation of mouse embryonic stem cells to dopamine neurons. Nanomedicine, 9(16); 2445-55.
82.Yang, H., Bremner, DH., Tao, L., Li, H., Hu, J., Zhu, L. (2016). Carboxymethyl chitosan-mediated synthesis of hyaluronic acid-targeted graphene oxide for cancer drug delivery. Carbohydrate Polymers, 135; 72-8.
83.Yoon, HH., Bhang, SH., Kim, T., Yu, T., Hyeon, T., Kim, BS. (2014). Dual Roles of Graphene oxide in chondrogenic differentiation of adult stem cells: cell‐adhesion substrate and growth factor‐delivery carrier. Advanced Functional Materials, 24(41); 6455-64.
84.Zhai, S., Yang, L., Cui, QC., Sun, Y., Dou, QP., Yan, B. (2010). Tumor cellular proteasome inhibition and growth suppression by 8-hydroxyquinoline and clioquinol requires their capabilities to bind copper and transport copper into cells. JBIC Journal of Biological Inorganic Chemistry, 15(2); 259-69.
85.Zhang, SL., Zhai, X., Zhang, SJ., Yu, HH., Gong, P. (2010). Synthesis and cytotoxicity studies of quinoline-3-carbonitrile derivatives. Chinese Chemical Letters, 21(8); 939-42.
86.Zhang, X., Yin, J., Peng, C., Hu, W., Zhu, Z., Li, W. (2011). Distribution and biocompatibility studies of graphene oxide in mice after intravenous administration. Carbon, 49(3); 986-95.
87.Zhang, Y., Ali, SF., Dervishi, E., Xu, Y., Li, Z., Casciano, D. (2010). Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS Nano, 4(6); 3181-6.
88.Zheng, XT., Ma, XQ., Li, CM. (2016). Highly efficient nuclear delivery of anti-cancer drugs using a bio-functionalized reduced graphene oxide. Journal of Colloid and Interface Science, 467; 35-42.
