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Cancer Chemotherapy and Pharmacology

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16.01.2019 | Original Article

Encapsulation of a new quinoxaline derivative in PLGA alters the pattern of its anticancer potency and induces apoptosis

verfasst von: Entsar A. Saad, Heba M. Waly

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2019

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Abstract

Purpose

Searching for novel anticancer therapeutics which are effective and primarily less toxic is urgently needed. Drug encapsulation provides more protection of drug within the body with more stable drug circulation levels thus avoiding drug peak-related adverse effects. We aimed first to develop and characterize a nano-particulate drug delivery system using poly(lactic-co-glycolic acid) (PLGA) for the new compound N-butylpyridoquinoxaline 1,4-dioxide (NBPQD), and second to investigate its anticancer effect and the probable mechanism.

Methods

NBPQD–PLGA nano-particles were prepared and their shape, size, zeta potential, encapsulation efficiency (EE%), drug loading (DL%), drug release, anticancer activity against six human cancer cell lines, DNA binding ability, and flow cytometric analyses of apoptosis, cell cycle and caspase-3 activity were investigated.

Results and conclusions

NBPQD–PLGA nano-particles were spherical with diameter around 54 nm. Zeta potential, EE%, and DL% values were − 20.4 mV, 88% and 21.8%, respectively. Nano-particles exhibited higher marked anticancer activities (much lower IC₅₀s) and changed the anticancer potency pattern towards all the studied cell lines compared to free NBPQD with superior potency against colorectal carcinoma (HCT-116, IC₅₀ of 12.2 µg/mL). NBPQD–PLGA acts by induction of cancer cell apoptosis through oxidative stress, DNA damage, and activating a caspase-3 signaling pathway.

El-Emshaty HM, Saad EA, Gouida MS, Elshahawy ZR (2018) Associations between CD133, CK19 and G2/M in cirrhotic HCV (genotype-4) patients with or without accompanying tumor. Biocell 42(2):55–60CrossRef

Attallah A, El-Far M, Abdel Malak C, Omran M, Farid K, Yahya R et al (2015) A simple diagnostic index comprising epithelial membrane antigen and fibronectin for hepatocellular carcinoma. Ann Hepatol 14:869–880CrossRefPubMed

Saad EA, Hassanien MM, Elneely EA (2017) Iron(III) diacetylmonoxime–2-hydrazinopyridine complex: a new prospective antitumor drug. Appl Organometal Chem 31(9):e3684. https://doi.org/10.1002/aoc.3684 CrossRef

Saad EA, Hassanien MM, El-Lban FW (2017) Nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex can inhibit Ehrlich solid tumor growth in mice: a potential new antitumor drug. Biochem Biophys Res Commun 484:579–585. https://doi.org/10.1016/j.bbrc.2017.01.137 CrossRefPubMed

Saad EA, Hassanien MM, El-Mezayen H, ELmenawy NM (2017) Regression of murine Ehrlich ascites carcinoma using synthesized cobalt complex. MedChemComm 8:1103–1111. https://doi.org/10.1039/C6MD00618C CrossRefPubMedPubMedCentral

Nagajyothi PC, Muthuraman P, Sreekanth TVM, Kim DH, Shim J (2017) Green synthesis: in-vitro anticancer activity of copper oxide nanoparticles against human cervical carcinoma cells. Arabian J Chem 10:215–225CrossRef

Wang H, Zhao Y, Wu Y, Hu Y, Nan K, Nie G et al (2011) Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials 32:8281–8290CrossRefPubMed

Dias DJS, Joanitti GA, Azevedo RB, Silva LP, Lunardi CN, Gomes AJ (2015) Chlorambucil encapsulation into PLGA nanoparticles and cytotoxic effects in breast cancer cell. J Biophysical Chem 6:1–13CrossRef

Al-Mutairi FM, Abdel-Daim MM, Ibrahim IT, Habib SA, Waly HM (2016) The potent effect of a newly synthesized N-Butylpyridoquinoxaline 1,4-dioxide (NBPQD) derivative as antitumor agent in solid tumor model. Int J Pharm Res Allied Sci 5:203–218

10.

Habib SA, Ibrahim IT, Abd-Eldaye MA, El-Sheshtawey MM, Waly HM (2012) N-Butylpyridoquinoxaline 1,4-dioxide (NBPQD) as a new potent for tumor imaging and therapy. Nat Sci 4:1074–1084

11.

Homan KA, Chen J, Schiano A, Mohamed M, Willets KA, Murugesan S et al (2011) Silver–polymer composite stars: synthesis and applications. Adv Funct Mater 21:1673–1680CrossRefPubMedPubMedCentral

12.

Li XL, Li RT, Qian X, Ding Y, Tu Y, Guo R, Hu Y et al (2008) Superior antitumor efficiency of cisplatin-loaded nanoparticles by intratumoral delivery with decreased tumor metabolism rate. Eur J Pharm Biopharm 70:726–734CrossRefPubMed

13.

Mauceri HJ, Hanna NN, Beckett MA, Gorski DH, Staba MJ, Stellato KA et al (1998) Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature 349:287–291CrossRef

14.

Burres NS, Frigo A, Rasmussen RR, McAlpine JB (1992) A colorimetric microassay for the detection of agents that interact with DNA. J Nat Prod 55:1582–1587CrossRefPubMed

15.

Jin H, Pi J, Yang F, Jiang J, Wang X, Bai H et al (2016) Folate-chitosan nanoparticles loaded with ursolic acid confer anti-breast cancer activities in vitro and in vivo. Sci Rep 6:30782. https://doi.org/10.1038/srep30782 CrossRefPubMedPubMedCentral

16.

Chuan L, Jia Z, Yu-Jiao Z, Shu-Fang N, Jun C, Qian W et al (2015) Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals. Chin J Nat Med 13:641–652PubMedCentral

17.

Borah A, Palaninathan V, Girija AR, Balasubramanian S, Rochani AK, Maekawa T (2017) Poly-lactic-co-glycolic acid nanoformulation of small molecule antagonist GANT61 for cancer annihilation by modulating hedgehog pathway. NanoWorld J 3:1–10CrossRef

18.

Lee MS, Dees EC, Wang AZ (2017) Nanoparticle-delivered chemotherapy: old drugs in new packages. Oncology J 31:198–208

19.

Heydari R, Rashidipour M (2015) Green synthesis of silver nanoparticles using extract of Oak fruit hull (jaft): synthesis and in vitro cytotoxic effect on MCF-7 cells. Int J Breast Cancer 846743:1–6CrossRef

20.

Ong SGM, Ming LC, Lee KS, Yuen KH (2016) Influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Pharmaceutics 8(3):25. https://doi.org/10.3390/pharmaceutics8030025 CrossRefPubMedCentral

21.

Liu D-q, Cheng Z-q, Feng Q-j, Li H-j, Ye S-f, Teng B (2018) Polycaprolactone nanofibres loaded with 20(S)-protopanaxadiol for in vitro and in vivo anti-tumour activity study. R Soc Open Sci 5(5):180137. https://doi.org/10.1098/rsos.180137 CrossRefPubMedPubMedCentral

22.

Saad EA, El-Gayar HA, El-Demerdash RS, Radwan KH (2018) Hepato-toxic risk of gum arabic during adenine-induced renal toxicity prevention. J Appl Pharm Sci 8(12):104–111. https://doi.org/10.7324/JAPS.2018.8801 CrossRef

23.

Saad EA, El-Gayar HA, El-Demerdash RS, Radwan KH (2018) Frankincense administration antagonizes adenine induced chronic renal failure in rats. Phcog Mag 14(58):634–640. https://doi.org/10.4103/pm.pm_271_18 CrossRef

24.

Habib SA, Saad EA, Elsharkawy AA, Attia ZR (2015) Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with obesity in Egyptian non-diabetic obese children and adolescents. Adv Med Sci 60:179–185CrossRefPubMed

25.

Saad EA, Habib SA, Refai WA, Elfayoumy AA (2017) Malondialdehyde, adiponectin, nitric oxide, C-reactive protein, tumor necrosis factor-alpha and insulin resistance relationships and inter-relationships in type 2 diabetes early stage. Is metformin alone adequate in this stage? Int J Pharm Pharm Sci 9(10):176–181. https://doi.org/10.22159/ijpps.2017v9i10.21149 CrossRef

26.

Saad EA, Hassanien MM, El-Hagrasy MA, Radwan KH (2015) Antidiabetic, hypolipidemic and antioxidant activities and protective effects of Punica granatum peels powder against pancreatic and hepatic tissues injuries in streptozotocin induced IDDM in rats. Int J Pharm Pharm Sci 7(7):397–402. https://innovareacademics.in/journals/index.php/ijpps/article/view/6705/2649

27.

Saad EA, Toson EA, Ahmed GM (2015) Clove or green tea administration antagonizes khat hepatotoxicity in rats. Int J Pharm Pharm Sci 7(6):72–76

28.

Saad EA, Habib SA (2013) Effect of crude extracts of some medicinal plants on the osmotic stability of human erythrocytes in vitro. J Free Rad Antioxidants Photon 139:265–272. https://sites.google.com/site/photonfoundationorganization/home/the-journal-of-freeradicals-and-antioxidants

29.

Toson EA, Habib SA, Saad EA, Harraz NH (2014) Toxic and anti-fertility effects of Alocasia macrorrhiza and Calotropis procera ethanolic extracts on male mice. Int J Biochem Photon 195:328–338. https://sites.google.com/site/photonfoundationorganization/home/internationaljournal

30.

Priyadarsini KI, Dennis MF, Naylor MA, Stratford MRL, Wardman P (1996) Free radical intermediates in the reduction of quinoxaline N-oxide antitumor drugs: redox and prototropic reactions. J Am Chem Soc 118:5648–5654CrossRef

31.

Xu Y, McSally J, Andricioaei I, Al-Hashimi HM (2018) Modulation of Hoogsteen dynamics on DNA recognition. Nature Comm 9:Article number: 1473. https://doi.org/10.1038/s41467-018-03516-1 CrossRef

32.

Azqueta A, Pachon G, Cascante M, Creppy EE, Lopez de Cerain A (2005) DNA damage induced by a quinoxaline 1,4-di-N-oxide derivative (hypoxic selective agent) in Caco-2 cells evaluated by the comet assay. Mutagenesis 20:165–171CrossRefPubMed

33.

Frankfurt OS, Krishan A (2003) Apoptosis-based drug screening and detection of selective toxicity to cancer cells. Antican Drugs 14:555–561CrossRef

34.

Elsayed SA, Saad EA, Mostafa SI (2018) Development of new potential anticancer metal complexes derived from 2-hydrazinobenzothiazole. Mini Rev Med Chem. https://doi.org/10.2174/1389557518666181017143548 CrossRefPubMed

35.

Feng Q, Liu Y, Huang J, Chen K, Huang J, Xiao K (2018) Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings. Sci Rep 8, Article number: 2082. https://doi.org/10.1038/s41598-018-19628-z CrossRefPubMedPubMedCentral

36.

Vaja F, Guran C, Ficai D, Ficai A, Oprea O (2014) Cytotoxic effects of ZnO nanoparticles incorporated in mesoporous silica. UPB Sci Bull 76:55–66

37.

Dickson MA, Schwartz GK (2009) Development of cell-cycle inhibitors for cancer therapy. Curr Oncol 16:36–43PubMedPubMedCentral

38.

Chen B, Yang J-Z, Wang L-F, Zhang Y-J, Lin X-J (2015) Ifosfamide-loaded poly (lactic-co-glycolic acid) PLGA-dextran polymeric nanoparticles to improve the antitumor efficacy in Osteosarcoma. BMC Cancer 15:752. https://doi.org/10.1186/s12885-015-1735-6 CrossRefPubMedPubMedCentral

39.

Mielcke TR, Muradás TC, Filippi-Chiela EC, Amaral MEA, Kist LW, Bogo MR et al (2017) Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones. Sci Rep 7:15850. https://doi.org/10.1038/s41598-017-16199-3 CrossRefPubMedPubMedCentral

40.

Singh SK, Lillard JW Jr, Singh R (2018) Reversal of drug resistance by planetary ball milled (PBM) nanoparticle loaded with resveratrol and docetaxel in prostate cancer. Cancer Lett 427:49–62. https://doi.org/10.1016/j.canlet.2018.04.017 CrossRefPubMedPubMedCentral

Titel: Encapsulation of a new quinoxaline derivative in PLGA alters the pattern of its anticancer potency and induces apoptosis
verfasst von: Entsar A. Saad
Heba M. Waly
Publikationsdatum: 16.01.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03770-0

Springer Medizin

Encapsulation of a new quinoxaline derivative in PLGA alters the pattern of its anticancer potency and induces apoptosis

Abstract

Purpose

Methods

Results and conclusions

Neu im Fachgebiet Onkologie

Erhöhte Mortalität bei postpartalem Brustkrebs

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

Bessere Prognose mit links- statt rechtsseitigem Kolon-Ca.

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results and conclusions

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