Abstract
Beneficial effects of MYC such as antioxidant, cytoprotective and antimicrobial activity have been investigated in various studies. The aim of the present research was to evaluate the poisonous impact of myricetin (MYC) that have been encapsulated in solid lipid nanoparticles (MYC-SLNs) on the growth of A549 human lungs adenocarcinoma cancer cells. A549 and MRC5 (healthy cells) cell lines were given with 25 μM of MYC or MYC-SLNs for 24 h and cell viability, colony formation, and gene expression were evaluated. The MYC-SLNs with appropriate characteristics (particle size of 89.23 ± 6.9 nm, Zeta potential of − 27.9 and entrapment efficiency of 69.2%) were prepared. Cytotoxicity evaluations demonstrated inhibition of the growth of A549 cells of a little IC50 (50% suppressive concentration) value via MYC-SLNs. Induction of a considerable decline of rapid growth and viability of A549 cells has been performed by MYC-SLNs. While a slight increase in the percentage of apoptosis was observed in the A549 cells, necrosis percentage was significantly increased by MYC-SLNs in comparison with the free MYC. Results showed that MYC-SLNs could upregulate the expression of necroptotic related genes such as RIPK3 and MLKL in the A549. MYC-SLNs or MYC did not influence proliferation, apoptosis, and viability of MRC5 cells. With regard to the findings, SLNs considerably augmented the poisonous impact of MYC versus cancer cells of human lungs.
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Abbasalipourkabir R, Salehzadeh A, Abdullah R (2010) Antitumor activity of tamoxifen loaded solid lipid nanoparticles on induced mammary tumor gland in Sprague-Dawley rats. Afr J Biotechnol 9:7337–7345. https://doi.org/10.5897/AJB10.628
Abd-Rabou AA, Ahmed HH (2017) PEG decorated PLGA nano-prototype for delivery of bioactive compounds: a novel approach for induction of apoptosis in HepG2 cell line. Adv Med Sci 62:357–367. https://doi.org/10.1016/j.advms.2017.01.003
Ahamed M, Akhtar MJ, Raja M, Ahmad I, Siddiqui MK, AlSalhi MS, Alrokayan SA (2011) ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress. Nanomedicine 7:904–913. https://doi.org/10.1016/j.nano.2011.04.011
Badawi NM, Teaima MH, El-Say KM, Attia DA, El-Nabarawi MA, Elmazar MM (2018) Pomegranate extract-loaded solid lipid nanoparticles: design, optimization, and in vitro cytotoxicity study. Int J Nanomed 13:1313–1326. https://doi.org/10.2147/IJN.S154033
Baek JS, Na YG, Cho CW (2018) Sustained cytotoxicity of wogonin on breast cancer cells by encapsulation in solid lipid nanoparticles. Nanomaterials 8:159–171. https://doi.org/10.3390/nano8030159
Cardaci S, Filomeni G, Rotilio G, Ciriolo MR (2008) Reactive oxygen species mediate p53 activation and apoptosis induced by sodium nitroprusside in SH-SY5Y cells. Mol Pharmacol 74:1234–1245. https://doi.org/10.1124/mol.108.048975
Cho Y, McQuade T, Zhang H, Zhang J, Chan FK (2011) RIP1-dependent and independent effects of necrostatin-1 in necrosis and T cell activation. PLoS ONE 6:23209–23217. https://doi.org/10.1371/journal.pone.0023209
Chromik J, Safferthal C, Serve H, Fulda S (2014) Smac mimetic primes apoptosis-resistant acute myeloid leukaemia cells for cytarabine-induced cell death by triggering necroptosis. Cancer Lett 344:101–109. https://doi.org/10.1016/j.canlet.2013.10.018
Colbert LE, Fisher SB, Hardy CW, Hall WA, Saka B, Shelton JW, Petrova AV, Warren MD, Pantazides BG, Gandhi K, Kowalski J, Kooby DA, El-Rayes BF, Staley CA 3rd, Adsay NV, Curran WJ Jr, Landry JC, Maithel Sk YuDS (2013) Pronecrotic mixed lineage kinase domain-like protein expression is a prognostic biomarker in patients with early-stage resected pancreatic adenocarcinoma. Cancer 119:3148–3155. https://doi.org/10.1002/cncr.28144
Devi KP, Rajavel T, Habtemariam S, Nabavi SF, Nabavi SM (2015) Molecular mechanisms underlying anticancer effects of myricetin. Life Sci 142:19–25. https://doi.org/10.1016/j.lfs.2015.10.004
Dhuriya YK, Sharma D (2018) Necroptosis: a regulated inflammatory mode of cell death. J Neuroinflamm 15:199–207. https://doi.org/10.1186/s12974-018-1235-0
Dondelinger Y, Aguileta MA, Goossens V, Dubuisson C, Grootjans S, Dejardin E, Vandenabeele P, Bertrand MJ (2013) RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition. Cell Death Differ 20:1381–1392. https://doi.org/10.1038/cdd.2013.94
Ekambaram P, Sathali AAH, Priyanka K (2012) Solid lipid nanoparticles: a review. Sci Rev Chem Commun 2:80–102
Ertao Z, Jianhui C, Kang W, Zhijun Y, Hui W, Chuanggi C, Changjiang Q, Sile C, Yulong H, Shirong C (2016) Prognostic value of mixed lineage kinase domain-like protein expression in the survival of patients with gastric cancer. Tumor Biol 37:13679–13685. https://doi.org/10.1007/s13277-016-5229-1
Eskandari M, Barar J, Dolatabadi JE, Hamishehkar H, Nazemiyeh H (2015) Formulation, characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles. Pharm Biol 53:1525–1538. https://doi.org/10.3109/13880209.2014.991836
Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C (2006) Clonogenic assay of cells in vitro. Nat Protoc 1:2315–2319. https://doi.org/10.1038/nprot.2006.339
Fu Z, Deng B, Liao Y, Shan L, Yin F, Wang Z, Zeng H, Zuo D, Hua Y, Cai Z (2013) The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis. BMC Cancer 13:580–589. https://doi.org/10.1186/1471-2407-13-580
Fulda S (2014) Therapeutic exploitation of necroptosis for cancer therapy. Semin Cell Dev Biol 35:51–56. https://doi.org/10.1016/j.semcdb.2014.07.002
Gaber DM, Nafee N, Abdallah OY (2017) Myricetin solid lipid nanoparticles: stability assurance from system preparation to site of action. Eur J Pharm Sci 109:569–580. https://doi.org/10.1016/j.ejps.2017.08.007
Hamishehkar H, Bahadori MB, Vandghanooni S, Eskandari M, Nakhlband A, Eskandari M (2018) Preparation, characterization and anti-proliferative effects of sclareol loaded solid lipid nanoparticles on A549 human lung epithelial cancer cells. J Drug Deliv Sci Technol 45:272–280. https://doi.org/10.1016/j.jddst.2018.02.017
Han W, Li L, Qiu S, Lu Q, Pan Q, Gu Y, Luo J, Hu X (2007) Shikonin circumvents cancer drug resistance by induction of a necroptotic death. Mol Cancer Ther 6:1641–1649. https://doi.org/10.1158/1535-7163.MCT-06-0511
Han Q, Ma Y, Wang H, Dai Y, Chen C, Liu Y, Jing L, Sun X (2018) Resibufogenin suppresses colorectal cancer growth and metastasis through RIP3-mediated necroptosis. J Transl Med 16:201–213. https://doi.org/10.1186/s12967-018-1580-x
Harnly JM, Doherty RF, Beecher GR, Holden JM, Haytowitz DB, Bhagwat S, Gebhardt S (2006) Flavonoid content of US fruits, vegetables and nuts. J Agric Food Chem 54:9966–9977. https://doi.org/10.1021/jf061478a
He L, Peng K, Liu Y, Xiong J, Zhu FF (2013) Low expression of mixed lineage kinase domain-like protein is associated with poor prognosis in ovarian cancer patients. Onco Targets Ther 6:1539–1543. https://doi.org/10.2147/OTT.S52805
Jain A, Garg NK, Jain A, Keshawarni P, Jain AK, Nirbhavane P, Tyagi RK (2016) A synergistic approach of adapalene-loaded nanostructured lipid carriers, and vitamin C co-administration for treating acne. Drug Dev Ind Pharm 42:897–905. https://doi.org/10.3109/03639045.2015.1104343
Jiang S, Zhu R, He X, Wang J, Wang M, Qian Y, Wang S (2016) Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles. Int J Nanomed 12:167–178. https://doi.org/10.2147/IJN.S12310
Jie H, He Y, Huang X, Zhou Q, Han Y, Li X, Bai Y, Sun E (2016) Necrostatin-1 enhances the resolution of inflammation by specifically inducing neutrophil apoptosis. Oncotarget 7:19367–19381. https://doi.org/10.18632/oncotarget.8346
Kamble SS, Gambhire MS, Gujar KN (2015) Optimization and development of candesartan cilexetil loaded solid lipid nanoparticle for the treatment of hypertension. J Pharm Biosci 3:53–64
Kim ME, Ha TK, Yoon JH, Lee JS (2014) Myricetin induces cell death of human colon cancer cells via BAX/BCL2-dependent pathway. Anticancer Res 34:701–706
Koo GB, Morgan MJ, Lee DJ, Kim WJ, Yoon JH, Koo JS, Kim SI, Kim SJ, Son MK, Hong SS, Levy JM, Da Pollyea, Jordan CT, Yan P, Frankhouser D, Nicolet D, Maharry K, Marcucci G, Choi KS, Cho H, Thorbum A, Ys Kim (2015) Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics. Cell Res 25:707–725. https://doi.org/10.1038/cr.2015.56
Laukens B, Jennewein C, Schenk B, Vanlangenakker N, Schier A, Cristofanon S, Zobel K, Deshayes K, Vucic D, Jeremias I, Bertrand MJ, Vandenabeele P, Fulda S (2011) Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor alpha-induced necroptosis. Neoplasia 13:971–979. https://doi.org/10.1593/neo.11610
Locatelli SL, Cleris L, Stirparo GG, Tartari S, Saba E, Pierdominici M, Malorni W, Carbone A, Anichini A, Carlo-Stella C (2014) BIM upregulation and ROS-dependent necroptosis mediate the antitumor effects of the HDACi Givinostat and Sorafenib in Hodgkin lymphoma cell line xenografts. Leukemia 28:1861–1871. https://doi.org/10.1038/leu.2014.81
Ma JW, Tsao TCY, His YT, Lin YC, Chen Y, Ho CT (2016) Essential oil of Curcuma aromatica induces apoptosis in human non-small-cell lung carcinoma cells. J Funct Foods 22:101–112. https://doi.org/10.1016/j.jff.2016.01.019
Morales P, Haza AI (2012) Selective apoptotic effects of piceatannol and myricetin in human cancer cells. J Appl Toxicol 32:986–993. https://doi.org/10.1002/jat.1725
Moriwaki K, Bertin J, Gough PJ, Orlowski GM, Chan FK (2015) Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death. Cell Death Dis 6:1636–1646. https://doi.org/10.1038/cddis.2015.16
Nabavi SM, Nabavi SF, Eslami S, Moghaddam AH (2012) In vivo protective effects of quercetin against sodium fluoride-induced oxidative stress in the hepatic tissue. Food Chem 132:931–935. https://doi.org/10.1016/j.foodchem.2011.11.070
Nabavi SF, Nabavi SM, Ebrahimzadeh MA, Eslami B, Jafari N (2013a) In vitro antioxidant and antihemolytic activities of hydroalcoholic extracts of Allium scabriscapum Boiss. & Ky. aerial parts and bulbs. Int J Food Prop 16:713–722. https://doi.org/10.1080/10942912.201.565902
Nabavi SF, Nabavi SM, Habtemariam S, Moghaddam AH, Sureda A (2013b) Hepatoprotective effect of gallic acid isolated from Peltiphyllum peltatum against sodium fluoride-induced oxidative stress. Ind Crop Prod 44:50–55. https://doi.org/10.1016/j.indcrop.2012.10.024
Nabavi SF, Nabavi SM, Setzer WN, Nabavi SA, Nabavi MA, Ebrahimzadeh MA (2013c) Antioxidant and antihemolytic activity of lipid-soluble bioactive substances in avocado fruits. Fruits 68:185–193. https://doi.org/10.1051/fruits/2013066
Nabavi SM, Marchese A, Izadi M, Curti V, Daglia M, Nabavi SF (2015a) Plants belonging to the genus Thymus as antibacterial agents: from farm to pharmacy. Food Chem 173:339–347. https://doi.org/10.1016/j.foodchem.2014.10.042
Nabavi SF, Russo GL, Daglia M, Nabavi SM (2015b) Role of quercetin as an alternative for obesity treatment: you are what you eat! Food Chem 179:305–310. https://doi.org/10.1016/j.foodchem.2015.02.006
Ni CH, Yu CS, Lu HF, Yang JS, Huang HY, Chen PY, Wu SH, Ip SW, Chiang SY, Lin JG, Chung JG (2014) Chrysophanol-induced cell death (necrosis) in human lung cancer A549 cells is mediated through increasing reactive oxygen species and decreasing the level of mitochondrial membrane potential. Environ Toxicol 29:740–749. https://doi.org/10.1002/tox.21801
Ong KC, Khoo HE (1997) Biological effects of myricetin. Gen Pharmacol 29:121–126. https://doi.org/10.1016/S0306-3623(96)00421-1
Park S, Hatanpaa KJ, Xie Y, Mickey BE, Madden CJ, Raisanen JM, Ramnarain DB, Xiao G, Saha D, Boothman DA, Zhao D, Bachoo RM, Pieper RO, Habib AA (2009) The receptor interacting protein 1 inhibits p53 induction through NF-kappaB activation and confers a worse prognosis in glioblastoma. Cancer Res 69:2809–2816. https://doi.org/10.1158/0008-5472.CAN-08-4079
Park KS, Chong Y, Kim MK (2016) Myricetin: biological activity related to human health. Appl Biol Chem 59:259–269. https://doi.org/10.1007/s13765-016-0150-2
Phillips PA, Sangwan V, Borja-Cacho D, Dudeja V, Vickers SM, Saluja AK (2011) Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3 K) signaling pathway. Cancer Lett 308:181–188. https://doi.org/10.1016/j.canlet.2011.05.002
Ruan J, Mei L, Zhu Q, Shi G, Wang H (2015) Mixed lineage kinase domain-like protein is a prognostic biomarker for cervical squamous cell cancer. Int J Clin Exp Pathol 8:15035–15038
Shih YW, Wu PF, Lee YC, Shi MD, Chiang TA (2009) Myricetin suppresses invasion and migration of human lung adenocarcinoma A549 cells: possible mediation by blocking the ERK signaling pathway. J Agric Food Chem 57:3490–3499. https://doi.org/10.1021/jf900124r
Steinhart L, Belz K, Fulda S (2013) Smac mimetic and demethylating agents synergistically trigger cell death in acute myeloid leukemia cells and overcome apoptosis resistance by inducing necroptosis. Cell Death Dis 4:802–814. https://doi.org/10.1038/cddis.2013.320
Stella B, Peira E, Dianzani C, Gallarate M, Battaglia L (2018) Development and characterization of solid lipid nanoparticles loaded with a highly active doxorubicin derivative. Nanomaterials 8:2–17. https://doi.org/10.3390/nano8020110
Su Z, Yang Z, Xie L, DeWitt JP, Chen Y (2016) Cancer therapy in the necroptosis era. Cell Death Differ 23:748–756. https://doi.org/10.1038/cdd.2016.8
Tahmasebi-Birgani MJ, Teimoori A, Ghadiri A, Mansouri-Asl H, Danyaei A, Khanbabaei H (2018) Fractionated radiotherapy might induce epithelial-mesenchymal transition and radioresistance in a cellular context manner. J Cell Biochem 120:8601–8610. https://doi.org/10.1002/jcb.28148
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11:700–714. https://doi.org/10.1038/nrm2970
Venkatramani R, Wang L, Malvar J, Dias D, Sposto R, Malogolowkin MH, Mascarenhas L (2012) Tumor necrosis predicts survival following neo-adjuvant chemotherapy for hepatoblastoma. Pediatr Blood Cancer 59:493–498. https://doi.org/10.1002/pbc.24038
Vijayakumar A, Baskaran R, Jang YS, Oh SH, Yoo BK (2017) Quercetin-loaded solid lipid nanoparticle dispersion with improved physicochemical properties and cellular uptake. AAPS PharmSciTech 18:875–883. https://doi.org/10.1208/s12249-016-0573-4
Voigt S, Philipp S, Davarnia P, Winoto-Morbach S, Roder C, Arenz C, Trauzold A, Kabelitz D, Schütze S, Kalthoff H, Adam D (2014) TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells. BMC Cancer 14:74–87. https://doi.org/10.1186/1471-2407-14-74
Wang Q, Chen W, Xu X, Li B, He W, Padilla MT, Jang JH, Nyunoya T, Amin S, Wang X, Lin Y (2013) RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species. Carcinogenesis 34:2119–2128. https://doi.org/10.1093/carcin/bgt143
Wang G, Wang JJ, Tang XJ, Du L, Li F (2016) In vitro and in vivo evaluation of functionalized chitosan–Pluronic micelles loaded with myricetin on glioblastoma cancer. Nanomedicine 12:1263–1278. https://doi.org/10.1016/j.nano.2016.02.004
Wang T, Jin Y, Yang W, Zhang L, Jin X, Liu X, He Y, Li X (2017a) Necroptosis in cancer: an angel or a demon? Tumor Biol 39:1–11. https://doi.org/10.1177/1010428317711539
Wang W, Zhang L, Chen T, Guo W, Bao X, Wang D, Ren B, Wang H, Li Y, Wang Y, Chen S, Tang B, Yang Q, Chen C (2017b) Anticancer effects of resveratrol-loaded solid lipid nanoparticles on human breast cancer cells. Molecules 22:1814–1914. https://doi.org/10.3390/molecules22111814
Wang W, Chen T, Xu H, Ren B, Cheng X (2018) Curcumin loaded solid lipid nanoparticles enhanced anticancer efficiency in breast cancer. Molecules 23:1578–1590. https://doi.org/10.3390/molecules23071578
Xu R, Zhang Y, Ye X, Xue S, Shi J, Chen Q (2013) Inhibition effects and induction of apoptosis of flavonoids on the prostate cancer cell line PC-3 in vitro. Food Chem 138:48–53. https://doi.org/10.1016/j.foodchem.2012.09.102
Yang H, Ma Y, Chen G, Zhou H, Yamazaki T, Klein C, Pietrocola F, Vacchelli E, Souguere S, Sauvat A, Zitvogel L, Kepp O, Kroemer G (2016) Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy. Oncoimmunology 5:1149673–1149675. https://doi.org/10.1080/2162402X.2016.1149673
Zhang X, Ling Y, Yu H, Ji Y (2010) Studies on mechanism of myricetin-induced apoptosis in human hepatocellular carcinoma HepG-2 cells. Zhongguo Zhong Yao Za Zhi 35:1046–1050
Zhang XH, Chen SY, Tang L, Shen YZ, Luo L, Xu CW, Liu Q, Li D (2013) Myricetin induces apoptosis in Hepg2 cells through Akt/P70s6 k/Bad signaling and mitochondrial apoptotic pathway. Anti-Cancer Agents Med Chem 13:1575–1581. https://doi.org/10.2174/1871520613666131125123059
Zheng AW, Chen YQ, Zhao LQ, Feng JG (2017) Myricetin induces apoptosis and enhances chemosensitivity in ovarian cancer cells. Oncol Lett 13:4974–4978. https://doi.org/10.3892/ol.2017.6031
Zhu WT, Liu SY, Wu L, Xu HL, Wang J (2017) Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer. Int J Nanomed 12:2621–2634. https://doi.org/10.2147/IJN.S128921
Żuryń A, Litwiniec A, Safiejko-Mroczka B, Klimaszewska A, Gagat M, Krajewski A, Gackowska L, Grzanka D (2016) The effect of sulforaphane on the cell cycle, apoptosis and expression of cyclin D1 and p21 in the A549 non-small cell lung cancer cell line. Int J Oncol 48:2521–2533. https://doi.org/10.3892/ijo.2016.3444
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The work described in this paper is a part of Ph.D. thesis of Atefeh Ashtari and was substantially supported by the Research Council of Ahvaz Jundishapur University of Medical Sciences, which are gratefully acknowledged.
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The study was supported by Grant CMRC-9623 from the Research Council of Ahvaz Jundishapur University of Medical Sciences.
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Layasadat Khorsandi, Esrafil Mansouri, Mohammad Rashno, Masoud Ali Karami and Atefeh Ashtari declare that they have no conflict of interest.
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Khorsandi, L., Mansouri, E., Rashno, M. et al. Myricetin Loaded Solid Lipid Nanoparticles Upregulate MLKL and RIPK3 in Human Lung Adenocarcinoma. Int J Pept Res Ther 26, 899–910 (2020). https://doi.org/10.1007/s10989-019-09895-3
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DOI: https://doi.org/10.1007/s10989-019-09895-3