A novel second-generation platinum derivative and evaluation of its anti-cancer potential
DOI:
https://doi.org/10.1590/s2175-97902022e20954Keywords:
Platinum-derivative, 4-hydroxybenzoic acid, Anti-cancer agent, Xenograft model, Lung cancerAbstract
Cisplatin is the primary anti-cancer agent for the treatment of most solid tumors. However, platinum-based anti-cancer chemotherapy produces severe side effects due to its poor specificity. There are a broad interest and literature base for a novel mechanism of action on platinum derivatives. Additionally, combining cisplatin with histone deacetylase inhibitors (HDACi) such as 4-hydroxybenzoic acid derivatives showed promising results in treating solid tumors. Here we aimed to conjugate 4-hydroxybenzoic acid with platinum to obtain a novel platinum derivative that can overcome cisplatin resistance. Cis-4-hydroxyphenylplatinum(II)diamine compound was synthesized under mild conditions and characterized. Cytotoxicity assay was performed on SKOV3-Luc and A549-Luc cells. Hemocompatibility and serum protein binding analysis were performed. Treatment potential was evaluated in xenograft tumor models. Biodistribution was tested on tumor-bearing mice via Pt analysis in organs with ICP-MS, ex vivo. In this study, cis-4-hydroxyphenylplatinum (II) diamine was synthesized with a yield of 62%. The MTT assay on A549-Luc and SKOV3-Luc cell lines resulted in IC50 values of 17.82 and 7.81 μM, respectively. While tumor growth was continued in the control group, the tumor volume decreased in the treatment group. All results point to the conclusion that the new compound has the potential to treat solid tumors.
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Alhareth K, Vauthier C, Gueutin C, Ponchel G, Moussa F. HPLC quantification of doxorubicin in plasma and tissues of rats treated with doxorubicin loaded poly(alkylcyanoacrylate) nanoparticles. J Chromatogr B Analyt Technol Biomed Life Sci. 2012;887-888:128-132.
Anilanmert B, Yalcin G, Arioz F, Dolen E. The spectrophotometric determination of cisplatin in urine, using o-phenylenediamine as derivatizing agent. Anal Lett. 2001;34(1):113-123.
Aranda FJ, Teruel JA, Ortiz A. Further aspects on the hemolytic activity of the antibiotic lipopeptide iturin A. Biochim Biophys Acta Biomembr. 2005;1713(1):51-56.
Arias M, Quijano JC, Haridas V, Gutterman JU, Lemeshko VV. Red blood cell permeabilization by hypotonic treatments, saponin, and anti-cancer avicins. Biochim Biophys Acta. 2010;1798(6):1189-1196.
Bohnert T, Gan LS. Plasma protein binding: From discovery to development. J Pharm Sci. 2013;102(9):2953-2994.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-254.
Caffrey PB, Frenkel GD. Prevention of carboplatin-induced resistance in human ovarian tumor xenografts by selenite. Anticancer Res. 2013;33(10):4249-54.
Chen Y, Janczuk A, Chen X, Wang J, Ksebati M, Wang PG. Expeditious syntheses of two carbohydrate-linked cisplatin analogs. Carbohydr Res. 2002;337(11):1043-6.
Cole AJ, David AE, Wang J, Galbán CJ, Hill HL, Yang VC. Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting. Biomaterials. 2011;32(8):2183-2193.
Cole WC, Wolf W. Preparation and metabolism of a cisplatin/ serum protein complex. Chem Biol Interact. 1980;30(2):223-235.
Czupryna J, Tsourkas A. Firefly Luciferase and Rluc8 Exhibit Differential Sensitivity to Oxidative Stress in Apoptotic Cells. PLoS One. 2011;6(5):e20073.
Dasari S, Tchounwou PB. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 2014;740:364-378.
Dhanani T, Shah S, Kumar S. A validated high performance liquid chromatography method for determination of three bioactive compounds p-hydroxy benzoic acid, negundoside and agnuside in Vitex species. Maced J Chem Chem Eng. 2015;34(2):321-331.
Esteban-Fernandez D, Verdaguer JM, Ramirez-Camacho R, Palacios MA, Gomez-Gomez MM. Accumulation, fractionation, and analysis of platinum in toxicologically affected tissues after cisplatin, oxaliplatin, and carboplatin administration. J Anal Toxicol. 2008;32(2):140-6.
Ho YP, Au-Yeung CFS, To Kenneth KW. Platinum-based anti-cancer agents: Innovative design strategies and biological perspectives. Med Res Rev. 2003;23(5):633-655.
Kutwin M, Sawosz E, Jaworski S, Kurantowicz N, Strojny B, Chwalibog A. Structural damage of chicken red blood cells exposed to platinum nanoparticles and cisplatin. Nanoscale Res Lett. 2014;9(1):257-257.
Liu W, Chen X, Ye Q, Hou S. 3-Hydroxycarboplatin, a simple carboplatin derivative endowed with an improved toxicological profile. Platinum Met Rev. 2012;56(4);248-256.
Mayer A, Vadon M, Rinner B, Novak A, Wintersteiger R, Fröhlich E. The role of nanoparticle size in hemocompatibility. Toxicology. 2009;258(2-3):139-147.
McKeage MJ, Morgan SE, Boxall FE, Murrer BA, Hard GC, Harrap KR. Lack of nephrotoxicity of oral ammine/amine platinum (IV) dicarboxylate complexes in rodents. Br J Cancer. 1993;67(5):996-1000.
Pasini A, Caldiroia C, Spinelli S, Valsecchi M. Comments on Different Synthetic Methods for the Preparation of Diammine and bis(Amine) Organodicarboxylatoplatinum(II) Complexes. Synth React Inorg Met -Org Chem. 1993;23(6):1021-1060.
Price PM, Yu F, Kaldis P, Aleem E, Nowak G, Safirstein RL, et al. Dependence of cisplatin-induced cell death in vitro and in vivo on cyclin-dependent kinase 2. J Am Soc Nephrol. 2006;17(9):2434-42.
Seidel C, Schnekenburger M, Dicato M, Diederich M. Antiproliferative and proapoptotic activities of 4-hydroxybenzoic acid-based inhibitors of histone deacetylases. Cancer Lett. 2014;343(1):134-46.
Semete B, Booysen L, Kalombo L, Ramalapa B, Hayeshi R, Swai HS. Effects of protein binding on the biodistribution of PEGylated PLGA nanoparticles post oral administration. Int J Pharm. 2012;424(1-2):115-120.
Wang L, Xiang S, Williams KA, Dong H, Bai W, Nicosia SV, et al. Depletion of HDAC6 enhances cisplatin-induced DNA damage and apoptosis in non-small cell lung cancer cells. PLoS One . 2012; 7(9):e44265.
Wang X, Guo Z. Targeting and delivery of platinum-based anti-cancer drugs. Chem Soc Rev. 2013;42(1):202-224.
Wang XN, Wang KY, Zhang XS, Yang C, Li XY. 4-Hydroxybenzoic acid (4-HBA) enhances the sensitivity of human breast cancer cells to adriamycin as a specific HDAC6 inhibitor by promoting HIPK2/p53 pathway. Biochem Biophys Res Commun. 2018;504(4):812-819.
Wong TS, Hashim Z, Zulkifli RM, Ismail HF, Zainol SN, Md Rajib NS, et al. LD50 Estimations for DiabecineTM Polyherbal Extracts Based on In Vitro Diabetic Models of 3T3-L1, WRL-68 and 1.1B4 Cell Lines. Chem Eng Trans. 2017;56:1567-1572.
Yallapu MM, Chauhan N, Othman SF, Khalilzad-Sharghi V, Ebeling MC, Khan S, et al. Implications of protein corona on physico-chemical and biological properties of magnetic nanoparticles. Biomaterials . 2015;46:1-12.
Yuan S, Ding X, Cui Y, Wei K, Zheng Y, Liu Y. Cisplatin Preferentially Binds to Zinc Finger Proteins Containing C3H1 or C4 Motifs. Eur J Inorg Chem. 2016;2017(12):1778-1784.
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