Antitumoral activity of micellar solutions containing allyl isothiocyanate: an in vitro study
Keywords:
allyl isothiocyanate, bladder cancer, micelles, poloxamerAbstract
Introduction: Several natural products exhibit promising antineoplastic activity against bladder cancer cells, including allyl isothiocyanate (AITC). However, the AITC irritates the mucous membranes and induces eczematous or vesicular skin reactions. Thus, pharmaceutical formulations are necessary to overcome these problems. The aim was to develop micellar solutions containing AITC and investigate their antitumoral activity in bladder carcinoma cell lines.
Method: The micellar solutions were prepared by cold dispersion method. Subsequently, we evaluated cytotoxicity, cell proliferation, cell cycle kinetics and long-term effects of micelles in bladder cancer cells.
Results: Cytotoxicity and cell proliferation assays showed there was an increase in AITC activity when it was encapsulated in micelles. We also observed cell cycle arrest in the S phase after treatment with AITC-micelles. Furthermore, the formulation was able to maintain the long-term effects of free AITC.
Conclusions: The micellar solutions developed can become an interesting approach for administration of AITC in the treatment of bladder cancer.
Downloads
References
Bray F, Ferlay J, Soerjomataram I, Siegel Rl, Torre LA, Jemal A. Global cancer statistics 2018: GLOBO¬CAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. doi: 10.3322/caac.21492.
Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortali¬ty: A global overview and recent trends. Eur Urol. 2017; 71(1):96-108. doi: 10.1016/j.eururo.2016.06.010.
Svátek RS, Hollenbeck BK, Holmäng S, Lee R, Kim SP, Stenzl A, Lotan Y. The economics of bladder cancer: costs and considerations of caring for this disease. Eur Urol. 2014; 66(2):253-262. doi: 10.1016/j.eururo.2014.01.006.
Hoskin P, Dubash S. Bladder conservation for muscle-invasive bladder cancer. Expert Rev Anticancer Ther. 2012; 12(8):1015-1020. doi: 10.1586/era.12.79.
Hoffman-Censits J, Choi W, Pal S, Trabulsi E, Kelly WK, Hahn NM, Mcconkey D, Comperat E, Matoso A, Cussenot O, Cancel-Tassin G, Fong MHY, Ross J, Madison R, Ali S. Urothelial cancers with small cell variant histology have confirmed high tumor mutational burden, frequent TP53 and RB mutations, and a unique gene expression profile. Eur Urol Oncol. 2020; S2588-9311(19):30168-3. doi: 10.1016/j.euo.2019.12.002.
Bose S, Banerjee S, Mondal A, Chakraborty U, Pumarol J, Croley CR, Bishayee A. Targeting the JAK/STAT signaling pathway using phytocompounds for cancer prevention and therapy. Cells. 2020; 9(6):E1451. doi: 10.3390/cells9061451.
Zhang D, Kanakkanthara A. Beyond the paclitaxel and vinca alkaloids: Next generation of plant-derived microtubule-targeting agents with potential anticancer activity. Cancers (Basel). 2020; 12(7):E1721. doi: 10.3390/cancers12071721.
Chang PY, Tsai FJ, Bau DT, Hsu YM, Yang JS, Tu MG, Chiang SI. Potential effects of allyl isothiocyanate on inhibiting cellular proliferation and inducing apoptotic pathway in human cisplatin-resistant oral cancer cells. J Formos Med Assoc. 2020; S0929-6646:30285-0. doi: 10.1016/j.jfma.2020.06.025.
Chen HE, Lin JF, Tsai TF, Lin YC, Chou KY, Hwang TI. Allyl isothiocyanate induces autophagy through the up-regulation of Beclin-1 in human prostate cancer cells. Am J Chin Med. 2018; 1-19. doi: 10.1142/S0192415X18500830.
Sávio ALV, Da Silva GN, Camargo EA, Salvadori DM. Cell cycle kinetics, apoptosis rates, DNA damage and TP53 gene expression in bladder cancer cells treated with allyl isothiocyanate (mustard essential oil). Mutat Res. 2014; 762:40–46. doi: 10.1016/j.mrfmmm.2014.11.004.
Li Y, Teng Z, Chen P, Song Y, Luo Y, Wang Q. Enhancement of aqueous stability of allyl isothiocyanate using nanoemulsions prepared by an emulsion inversion point method. J Colloid Interface Sci. 2015; 438:130-137. doi: 10.1016/j.jcis.2014.09.055.
Keskin D, Tezcaner A. Micelles as delivery system for cancer treatment. Curr Pharm Des. 2017; 23(35):5230-5241. doi: 10.2174/1381612823666170526102757.
Kalyane D, Raval N, Maheshwari R, Tambe V, Kalia K, Tekade RK. Employment of enhanced per¬meability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. Mater Sci Eng C Mater Biol Appl. 2019; 98:1252-1276. doi: 10.1016/j.msec.2019.01.066.
Barichello JM, Da Silva GN, Almeida TC. Universidade Federal de Ouro Preto. Sistema micelar ter-moreversível de poloxâmero 407 e alil isotiocianato, processo de obtenção, composição farmacêutica e uso. Brazil patent BR1020170118592; 2017.
Pelosi C, Chiron F, Dubs F, Hedde M, Ponge JF, Salmon S, Cluzeau D, Nélieu S. A new method to mea¬sure allyl isothiocyanate (AITC) concentrations in mustard - Comparison of AITC and commercial mus¬tard solutions as earthworm extractants. Appl Soil Ecol. 2014; 80:1–5. doi: 10.1016/j.apsoil.2014.03.005
Almeida TC, Guerra CCC, De Assis BLG, De Oliveira Aguiar Soares RD, Garcia CCM, Lima AA, Da Sil¬va GN. Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status. Environ Mol Mutagen. 2019; 60(8):740-751. doi: 10.1002/em.22297.
Bhattacharya A, Tang L, Li Y, Geng F, Paonessa JD, Chen SC, Wong MKK, Zhang Y. Inhibition of blad¬der cancer development by allyl isothiocyanate. Carcinogenesis. 2010; 31(2):281-286. doi: 10.1093/car-cin/bgp303.
Lewis SA. Everything you wanted to know about the bladder epithelium but were afraid to ask. Am J Physiol Renal Physiol. 2010; 278(6):867-874. doi: 10.1152/ajprenal.2000.278.6.F867.
Mantovani F, Collavin L, Del Sal G. Mutant p53 as a guardian of the cancer cell. Cell Death Differ. 2019; 26:199-212. doi: 10.1038/s41418-018-0246-9
Zarrintaj P, Ramsey JD, Samadi A, Atoufi Z, Yazdi MK, Ganjali MR, Amirabad LM, Zangene E, Farokhi M, Formela K, Saeb MR, Mozafari M, Thomas S. Poloxamer: A versatile tri-block copolymer for biomedi¬cal applications. Acta Biomater. 2020; 110:37-67. doi: 10.1016/j.actbio.2020.04.028
Owen SC, Chan DPY, Shoichet MS. Polymeric micelle stability. Nano Today. 2012; 7(1):53-65. doi: 10.1016/j.nantod.2012.01.002
Stammet M; Kwon GS, Rao DA. Drug loading in Pluronic® micelles made by solvent casting and equilibrium methods using resveratrol as a model drug. J Control Release. 2010; 148(1):21-56. doi: 10.1016/j.jconrel.2010.07.056.
Zhang Y, Huang Y, Li S. Polymeric micelles: nanocarriers for cancer-targeted drug delivery. AAPS PharmSciTech. 2014; 15(4):862-871. doi: 10.1208/s12249-014-0113-z
Fang J, Nakamura H, Maeda H. The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev. 2011; 63(3):136-151. doi: 10.1016/j.addr.2010.04.009.
Davis ME, Chen Z, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008; 7(9):771-782. doi: 10.1038/nrd2614.
Wei CC, Ge ZQ. Influence of electrolyte and poloxamer 188 on the aggregation kinetics of solid lipid nanoparticles (SLNs). Drug Dev Ind Pharm. 2012; 38:1084-1089. doi :10.3109/03639045.2011.640331.
Hientz K, Mohr A, Bhakta-Guha D, Efferth T. 2017. The role of p53 in cancer drug resistance and tar¬geted chemotherapy. Oncotarget. 2017; 8(5):8921-8946. doi: 10.18632/oncotarget.13475.
Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol. 2015; 16(7):393-405. doi: 10.1038/nrm4007.
Da Silva GN, Camargo EA, Salvadori DMF. Toxicogenomic activity of gemcitabine in two TP53-mu¬tated bladder cancer cell lines: special focus on cell cycle-related genes. Mol Biol Rep. 2012; 39:10373-10382. doi: 10.1007/s11033-012-1916-1
Chen NG, Chen KT, Lu CC, Lan YH, Lai CH, Chung YT, Yang JS, Lin YC. Allyl isothiocyanate triggers G2/M phase arrest and apoptosis in human brain malignant glioma GBM 8401 cells through a mito¬chondria-dependent pathway. Oncol Rep. 2010; 24(2):449-455. doi: 10.3892/or_00000878.
Lau WS, Chen T, Wong YS. Allyl isothiocyanate induces G2/M arrest in human colorectal adenocar¬cinoma SW620 cells through down-regulation of Cdc25B and Cdc25C. Mol Med Rep. 2010; 3:1023-1030. doi: 10.3892/mmr.2010.363
Tsai SC, Huang WW, Huang WC, Lu CC, Chiang JH, Peng SF, Chung JG, Lin YH, Hsu YM, Amagaya S, Yang JS. ERK-modulated intrinsic signaling and G(2)/M phase arrest contribute to the induction of apoptotic death by allyl isothiocyanate in MDA-MB-468 human breast adenocarcinoma cells. Int J On¬col. 2012; 41(6):2065-2072. doi: 10.3892/ijo.2012.1640.
Laskey RA, Fairman MP, Blow JJ. S phase of the cell cycle. Science. 1989; 246:609-614. doi: 10.1126/science.2683076.
Geng F, Tang L, Li Y, Yang L, Choi KS, Kazim AL, Zhang Y. Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation. J Biol Chem. 2011; 286(37):32259-32267. doi: 10.1074/jbc.M111.278127.
Munshi A, Hobbs M, Meyn RE. Clonogenic cell survival assay. Methods Mol Med. 2005; 110:21-28. doi: 10.1385/1-59259-869-2:021.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2020 Tamires Almeida, Daiane Oliveira, André Luiz Sávio, Fernanda Perasoli, Glenda Da Silva, José Mário Barichello
![Creative Commons License](http://i.creativecommons.org/l/by-nc-sa/4.0/88x31.png)
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The articles, which are published in this journal, are subject to the following terms in relation to the rights of patrimonial or exploitation:
- The authors will keep their copyright and guarantee to the journal the right of first publication of their work, which will be distributed with a Creative Commons BY-NC-SA 4.0 license that allows third parties to reuse the work whenever its author, quote the original source and do not make commercial use of it.
b. The authors may adopt other non-exclusive licensing agreements for the distribution of the published version of the work (e.g., deposit it in an institutional telematic file or publish it in a monographic volume) provided that the original source of its publication is indicated.
c. Authors are allowed and advised to disseminate their work through the Internet (e.g. in institutional repositories or on their website) before and during the submission process, which can produce interesting exchanges and increase citations of the published work. (See The effect of open access).