Hakkı İsmail KAYA, Ceren BOGUSLU, Esra KABAK, Cagla AKKOL, Ece Tuğba SAKA, Selcen ÇELİK UZUNER

The effect of silicon phthalocyanine on cell death and mitochondrial membrane potential in pancreatic cancer cells

Silicon (SiPcs) phthalocyanines are advantageous because they do not aggregate due to their special structural features. Therefore, they have been widely used in a range of areas in chemical and biological technology. One of the common applications is the use of phthalocyanines on cancer therapies. Pancreas cancer is one of the most common cancers with a high rate of mortality around the world. In this study we therefore aimed to investigate the potential of SiPcs molecules which we previously synthesized for the first time, on increased cell death and the effect on mitochondrial activity in pancreatic cancer cells. The results showed the significantly selective cytotoxic effect of SiPc on cancer cells compared to normal cells. Mitochondrial membrane potential was not different in cancer cells but in normal cells after SiPcs treatment. Pre-incubation time (24h) of SiPcs before light irradiation induced more significant cytotoxicity in pancreatic cancer cells but not in normal cells compared to prolonged pre-incubation (48). This study revisited the biological function of previously synthesized SiPcs, and the results conclude the cytotoxic activity of SiPcs on pancreas cancer. These preliminary findings can be extended for other cancer types and detailed with in vivo models in the future.

Keywords:

silicon phthalocyanine, cancer, cytotoxicity, mitochondrial membrane potential,

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[1]L. Kilmmert, D. Haarer,PresentLimits of Data Storage using Dye Molecules in Solid Matrices,Advanced Mater, 7, 1995, 495.
[2] J.W. Gardner, M.Z. Iskandari, B. Bott, Effect of electrodegeometry on gas sensitivity of lead phthalocyanine thin films,SensorsandActuators B: Chemical, 9, 1992, 133.
[3] R. Rellaa, A. Rzzob, A. Licciullic, P. Sicilianoa, L. Troisid, L. Vallic,Tests in controlledatmosphere on new optical gas sensing layers based on TiO2/metal phthalocyanine hybrid system, Materials Science and Engineering: C, 22, 2002, 439.
[4] F.Z. Henari,Optical switching in organometallic phthalocyanine, Journal of Optics A: Pureand Applied Optics, 3, 2001, 188.
[5] M. A. El Sallam, H.M. Mallah, D.G. Damhogi, E. Elesh, Thermal Analysis, DielectricResponseandElectricalConductivity of SiliconPhthalocyanineDichloride (SiPcCl 2 ) ThinFilms, Journal of Electronic Materials, 50, 2021, 562-570.
[6] I. Omeroglu, M. Goksel, V. Kussovski, V. Mantareva, M. Durmus, NovelWater-SolubleSilicon(IV) PhthalocyanineforPhotodynamicTherapyandAntimicrobialInactivations, Macroheterocycles, 12 , 2019,255-263.
[7] G. Dilber, A. Nas, Z. Bıyıklıoglu, New octa-benzothiazolesubstituted metal freeandmetallophthalocyanines: Synthesis, characterizationandelectrochemicalstudies, TurkishJournal of AnalyticalChemistry, 3, 2021, 33-38.
[8] E. Bagda, Therecentstudiesabouttheinteraction of phthalocyanineswith DNA, TurkishJournal of AnalyticalChemistry, 3, 2021, 9-18.
[9] G. Sarkı, H. Yalazan, H. Kantekin, Synthesisandaggregationproperties of 2,9,16,23–tetrakis(chloro)-3,10,17,24–tetrakis[2-(4-allyl-2-methoxyphenoxy)ethoxy]phthalocyaninatocobalt(II), manganese(III), zinc(II) , TurkishJournal of AnalyticalChemistry, 2, 2020, 75-80.
[10]Y. Caglar, E.T. Saka, A novelsiliconephthalocyanineforthepreconcentrationandspectrophotometricdetermination of copperbyionicliquid-baseddispersiveliquid-liquidmicroextraction, TurkishJournal of AnalyticalChemistry, 1, 2019.
[11] E.T.Saka, H. Yalazan, Z. Bıyıklıoglu, H. Kantekin, K. Tekintas, Synthesis, aggregation, photocatalyticalandelectrochemicalproperties of axially 1-benzylpiperidin-4-oxy unitssubstitutedsiliconphthalocyanine, JournalofMolecularStructure, 1199,2020,126994.
[12] J. Huang, V. Lok, C. H.Ngai, L. Zhang, J. Yuan, X. Q. Lao, K. Ng, C.Chong, Z.J. Zheng, M. C S Wong, WorldwideBurden of, Risk Factorsfor, andTrends in PancreaticCancer, Gastroenterology, 160(3), 2021, 744-754.
[13] L. B. OliveiradeSiqueira, A.P. Santos Matos, M. R. MattosdaSilva, S. RochaPinto, R. S. Oliveira, E. R. Júnior,Pharmaceuticalnanotechnologyappliedtophthalocyaninesforthepromotion of antimicrobialphotodynamictherapy: A literaturereview, PhotodiagnosisandPhotodynamicTherapy, 39, (2022), 102896.
[14] C. Sarı, A. Nalçaoğlu, İ. Değirmencioğlu, F. Celep Eyüboğlu, Tumor-selectivenewpiperazine-fragmentedsiliconphthalocyaninesinitiatecelldeath in breastcancercelllines, Journal of PhotochemistryandPhotobiology B: Biology, 216, (2021), 112143.
[15] E.C. Aniogo, B.P.A. George, H. Abrahamse, PhthalocyanineinducedphototherapycoupledwithDoxorubicin; a promisingnoveltreatmentforbreastcancer, ExpertReview of AnticancerTheraphy, 17, (2017), 693-702.
[16] Q. Cui, S. Wen, P. Huang, Targetingcancercellmitochondria as a therapeuticapproach: recentupdates, FutureMedicinalChemistry, 9, (2017), 929-949.
[17]M. J. Stillman, T. Nyokong, Phthalocyanines: Propertiesand Applications, Editor: C. C. Leznoff, 1989, USA, VCH Publishers.
[18] D.D. Perrin, W.L.F. Armarego, Purification of LaboratoryChemicals, second ed., PergamonPress, Oxford, 1989.
[19] S. Celik-Uzuner, E. Birinci, S. Tetikoğlu, C. Birinci, S. Kolaylı, DistinctEpigeneticReprogramming, MitochondrialPatterns, Cellular Morphology, andCytotoxicityafterBeeVenomTreatment, RecentPatents on Anti-CancerDrugDiscovery, 16.3 (2021), 377-392.
[20] K. Mitra, M. C. T. Hartman, Siliconphthalocyanines: synthesisandresurgentapplications, OrganicandBiomolecularChemistry, 6, (2021), 1168-1190.
[21]Q. Liu, M.P. Mang, S.H. Tan, J. Wang, Q.L. Chen, K. Wang, W.J. Wu, Z.Y. Hong, Potent peptide-conjugatedsiliconphthalocyaninesfortumorphotodynamictherapy,Journal of Cancer, 9, (2018) 310-320.
[22] K. Li, W.Y. Dong, Q.Z. Liu, G.C. Lv, M.H. Xie, X.C. Sun, L. Qui, J.G. Lin, Journal of Photochemistry and Photobiology B-Biology, 190, (2019) 1-7.
[23] P. Sen, T. Nyokong, A novel axially palladium(II)-Schiff base complexsubstitutedsilicon(IV) phthalocyanine: Synthesis, characterization, photophysicochemical properties and photodynamic antimicrobial chemotherapy activityagainstStaphylococcusaureus, Polyhedron, 173, (2019) 114135.
[24] W.Y. Dong, K. Li, S.J. Wang, L. Qui, M.H. Xie, J.G. Lin, Current Pharmaceutical Chemistry, 22, (2021) 414-422.
[25] J.P. Taquet, C. Frochot, V. Manneville, M. Heyop-Barberi, Phthalocyaninescovalentlyboundtobiomoleculesfor a targeted photodynamic therapy, Current medicinal Chemistry, 14, (2007) 1673-1687.
[26] B. Aru, A. Günay, E. Senkuytu, G. Yanıkkaya-Demirel, A.G. Gürek, D. Atilla, A TranslationalStudy of a SiliconPhthalocyanineSubstitutedwith a HistoneDeacetylaseInhibitorforPhotodynamicTherapy, ACS Omega, 40, (2020) 25854–25867.
[27] J. Schmidt, W. Kuzyniak, J. Berkholz, G. Steinemann, R. Ogbodu, B. Hoffmann, G. Nouailles, A.G. Gürek, B. Nitzsche, M. Höpfner, Novelzinc andsilicon phthalocyanines as photosensitizersforphotodynamictherapy of cholangiocarcinoma, International Journal ofMolecularMedicine, 42, (2018) 534-546.
[28] B. Zhang, D. Wang, F. Guo, C. Xuan, Mitochondrialmembranepotentialandreactiveoxygenspecies in cancerstemcells, FamCancer, 14(1), (2015) 19-23.
[29] S.M. Malahingam, J.D.Ordaz, P.S. Low, Targeting of a PhotosensitizertotheMitochondrionEnhancesthePotency of PhotodynamicTherapy, ACS Omega, 6, (2018) 6066–6074.
[30] A. Al Fraj, A.S. Shaik, S. Afzal, S. Al-Muhsen, R. Halwani, Specifictargetingandnoninvasivemagneticresonanceimaging of an asthmabiomarker in thelungusingpolyethyleneglycolfunctionalizedmagneticnanocarriers, Contrast Media andMolecularImaging, 11, (2016) 172-183.
[31] K. Mitra, M. Samso, C.E. Lyons, M.C.T. Hartman, Hyaluronicacidgraftednanoparticles of a platinum(ii)–silicon(iv) phthalocyanineconjugatefortumorandmitochondria-targetedphotodynamictherapy in redlight, Journal of MaterialsChemistry B, 6 (2018) 7373-7377.