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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Photodynamic Effects of Vitamin K3 on Cervical Carcinoma Cells Activating Mitochondrial Apoptosis Pathways

Author(s): Yong Xin, Wenwen Guo, Chunsheng Yang, Qian Huang, Pei Zhang, Longzhen Zhang and Guan Jiang*

Volume 21, Issue 1, 2021

Published on: 14 August, 2020

Page: [91 - 99] Pages: 9

DOI: 10.2174/1871520620666200814164629

Price: $65

Abstract

Background: Photodynamic Therapy (PDT) is a photoactivation or photosensitization process, wherein vitamin K3 (Vit K3) serves as a photosensitizer to produce Reactive Oxygen Species (ROS) against bacteria at appropriate wavelengths. In this study, we used Vit K3 treatment combined with Ultraviolet radiation A (UVA) to produce photodynamic effects on cervical cancer.

Methods: The dose-concentration relationship between Vit K3 treatment and UVA on tumor cells was analyzed through the Cell Counting Kit-8 method. Then, the morphological characteristics of apoptosis cells were observed through fluorescent staining and fluorescence microscopy. Apoptosis after treatment with Vit K3 treatment, UVA, and Vit K3 treatment plus UVA was further observed through Western blot analysis, flow cytometry, and TUNEL assay. The xenograft models from HeLa cells were established for the exploration of the photodynamic effect of Vit K3 treatment on cervical cancer in vivo.

Results: Vit K3 treatment plus UVA reduced tumor cell viability in a dose-dependent manner. Further studies indicated that Vit K3 treatment plus UVA can inhibit tumor growth and enhance the apoptosis of cervical cancer cells. In the combination group, the expression levels of cleaved caspase-3, cleaved caspase-9, B-cell lymphoma- extra large (Bcl-xl), and cytochrome c (cyt-c) increased obviously, whereas the expression level of Bcell lymphoma 2 (Bcl-2) decreased relative to the expression levels of UVA- or Vit K3-treated cells. In the in vivo experiments, tumor growth was inhibited significantly in the VitK3 treatment plus UVA group. Additionally, we demonstrated that the combination therapy mediated an increase in cleaved caspase-3 and cleaved caspase-9 expression and decrease in Bcl-2 expression in vivo.

Conclusion: Our results showed that Vit K3 treatment combined with UVA exerted photodynamic effects on cervical cancer cells by activating mitochondrial apoptosis pathways.

Keywords: Vitamin K3, photodynamic therapy, photosensitizer, cervical cancer, apoptosis, caspase-9.

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[1]
Sadalla, J.C.; Andrade, J.M.; Genta, M.L.; Baracat, E.C. Cervical cancer: What’s new? Rev. Assoc. Med. Bras. (1992) 2015, 61(6), 536-542.
[http://dx.doi.org/10.1590/1806-9282.61.06.536] [PMID: 26841164]
[2]
Cohen, P.A.; Jhingran, A.; Oaknin, A.; Denny, L. Cervical cancer. Lancet, 2019, 393(10167), 169-182.
[http://dx.doi.org/10.1016/S0140-6736(18)32470-X] [PMID: 30638582]
[3]
Atif, M. Preliminary study of spectral features of normal and malignant cell cultures. Laser Phys., 2016, 26(4)
[http://dx.doi.org/10.1088/1054-660X/26/4/045601]
[4]
Atif, M.; Firdous, S.; Khurshid, A. In vitro study of 5-aminolevulinic acid-based photodynamic therapy for apoptosis in human cervical HeLa cell line. Laser Phys. Lett., 2009, 6(12), 886-891.
[5]
Tsikouras, P.; Zervoudis, S.; Manav, B.; Tomara, E.; Iatrakis, G.; Romanidis, C.; Bothou, A.; Galazios, G. Cervical cancer: Screening, diagnosis and staging. J. BUON, 2016, 21(2), 320-325.
[PMID: 27273940]
[6]
Sharma, C.; Deutsch, I.; Horowitz, D.P.; Hershman, D.L.; Lewin, S.N.; Lu, Y.S.; Neugut, A.I.; Herzog, T.J.; Chao, C.K.; Wright, J.D. Patterns of care and treatment outcomes for elderly women with cervical cancer. Cancer, 2012, 118(14), 3618-3626.
[http://dx.doi.org/10.1002/cncr.26589] [PMID: 22038773]
[7]
Chen, J.; Gu, W.; Yang, L.; Chen, C.; Shao, R.; Xu, K.; Xu, Z.P. Nanotechnology in the management of cervical cancer. Rev. Med. Virol., 2015, 25(Suppl. 1), 72-83.
[http://dx.doi.org/10.1002/rmv.1825] [PMID: 25752817]
[8]
Yu, Y.; Xu, S.; You, H.; Zhang, Y.; Yang, B.; Sun, X.; Yang, L.; Chen, Y.; Fu, S.; Wu, J. In vivo synergistic anti-tumor effect of paclitaxel nanoparticles combined with radiotherapy on human cervical carcinoma. Drug Deliv., 2017, 24(1), 75-82.
[http://dx.doi.org/10.1080/10717544.2016.1230902] [PMID: 28155566]
[9]
Conte, C.; Maiolino, S.; Pellosi, D.S.; Miro, A.; Ungaro, F.; Quaglia, F. Polymeric nanoparticles for cancer photodynamic therapy. Top. Curr. Chem. (Cham), 2016, 370, 61-112.
[http://dx.doi.org/10.1007/978-3-319-22942-3_3] [PMID: 26589506]
[10]
Rkein, A.M.; Ozog, D.M. Photodynamic therapy. Dermatol. Clin., 2014, 32(3), 415-425.
[http://dx.doi.org/10.1016/j.det.2014.03.009] [PMID: 24891062]
[11]
Eshghi, H.; Sazgarnia, A.; Rahimizadeh, M.; Attaran, N.; Bakavoli, M.; Soudmand, S. Protoporphyrin IX-gold nanoparticle conjugates as an efficient photosensitizer in cervical cancer therapy. Photodiagn. Photodyn. Ther., 2013, 10(3), 304-312.
[http://dx.doi.org/10.1016/j.pdpdt.2013.02.003] [PMID: 23993857]
[12]
Garg, T.; Jain, N.K.; Rath, G.; Goyal, A.K. Nanotechnology-based photodynamic therapy: Concepts, advances, and perspectives. Crit. Rev. Ther. Drug Carrier Syst., 2015, 32(5), 389-439.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.201501164] [PMID: 26559433]
[13]
Abrahamse, H.; Hamblin, M.R. New photosensitizers for photodynamic therapy. Biochem. J., 2016, 473(4), 347-364.
[http://dx.doi.org/10.1042/BJ20150942] [PMID: 26862179]
[14]
Calixto, G.M.; Bernegossi, J.; de Freitas, L.M.; Fontana, C.R.; Chorilli, M. Nanotechnology-based drug delivery systems for photodynamic therapy of cancer: A review. Molecules, 2016, 21(3), 342.
[http://dx.doi.org/10.3390/molecules21030342] [PMID: 26978341]
[15]
Yu, M.; Guo, F.; Wang, J.; Tan, F.; Li, N. Photosensitizer-loaded pH-responsive hollow gold nanospheres for single light-induced photothermal/photodynamic therapy. ACS Appl. Mater. Interfaces, 2015, 7(32), 17592-17597.
[http://dx.doi.org/10.1021/acsami.5b05763] [PMID: 26248033]
[16]
Benito, M.; Martín, V.; Blanco, M.D.; Teijón, J.M.; Gómez, C. Cooperative effect of 5-aminolevulinic acid and gold nanoparticles for photodynamic therapy of cancer. J. Pharm. Sci., 2013, 102(8), 2760-2769.
[http://dx.doi.org/10.1002/jps.23621] [PMID: 23712859]
[17]
Iqbal, S.; Fakhar-e-Alam, M. Photodynamic therapy, facile synthesis, and effect of sintering temperature on the structure, morphology, optical properties, and anticancer activity of Co3O4 nanocrystalline materials in the HepG2 cell line. J. Photochem. Photobiol. Chem. 2020, 386, 112130.
[http://dx.doi.org/10.1016/j.jphotochem.2019.112130]
[18]
Iqbal, S.; Fakhar-e-Alam, M. Structural, morphological, antimicrobial, and in vitro photodynamic therapeutic assessments of novel Zn+2-substituted cobalt ferrite nanoparticles. Results Phys., 2019, 15102529
[http://dx.doi.org/10.1016/j.rinp.2019.102529]
[19]
Akram, M.W.; Raziq, F.; Fakhar-e-Alam, M.; Aziz, M.H.; Alimgeer, K.S.; Atif, M.; Amir, M.; Hanif, A.; Farooq, W.A. Tailoring of Au-TiO2 nanoparticles conjugated with doxorubicin for their synergistic response and photodynamic therapy applications. J. Photochem. Photobiol. Chem., 2019, 384112040
[http://dx.doi.org/10.1016/j.jphotochem.2019.112040]
[20]
Iqbal, S.; Fakhar-e-Alam, M. Application of silver oxide nanoparticles for the treatment of cancer. J. Mol. Struct., 2019, 1189, 203-209.
[http://dx.doi.org/10.1016/j.molstruc.2019.04.041]
[21]
Peng, L. Syntheses and application of vitamin K3. Ch. J. Vet. Drug, 2003, 37(10), 50-52.
[22]
Bonilla-Porras, A.R.; Jimenez-Del-Rio, M.; Velez-Pardo, C. Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism. Cancer Cell Int., 2011, 11, 19.
[http://dx.doi.org/10.1186/1475-2867-11-19] [PMID: 21663679]
[23]
Shi, S.; Zheng, G.; Yang, C.; Chen, X.; Yan, Q.; Jiang, F.; Jiang, X.; Xin, Y.; Jiang, G. Effects of vitamin K3 combined with UVB on the proliferation and apoptosis of cutaneous squamous cell carcinoma A431 cells. OncoTargets Ther., 2019, 12, 11715-11727.
[http://dx.doi.org/10.2147/OTT.S228792] [PMID: 32099380]
[24]
Xu, F.; Vostal, J.G. Inactivation of bacteria via photosensitization of vitamin K3 by UV-A light. FEMS Microbiol. Lett., 2014, 358(1), 98-105.
[http://dx.doi.org/10.1111/1574-6968.12544] [PMID: 25053393]
[25]
Chen, Y.; Li, W.; Zhou, J.; Wen, Y.; Miao, X.; Xiong, L. Molecular mechanism of photodynamic therapy. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2014, 39(1), 102-108.
[PMID: 24473379]
[26]
Topaloglu, N.; Guney, M.; Aysan, N.; Gulsoy, M.; Yuksel, S. The role of reactive oxygen species in the antibacterial photodynamic treatment: Photoinactivation vs proliferation. Lett. Appl. Microbiol., 2016, 62(3), 230-236.
[http://dx.doi.org/10.1111/lam.12538] [PMID: 26671847]
[27]
Bartosz, G. Reactive oxygen species: Destroyers or messengers? Biochem. Pharmacol., 2009, 77(8), 1303-1315.
[http://dx.doi.org/10.1016/j.bcp.2008.11.009] [PMID: 19071092]
[28]
Buytaert, E.; Dewaele, M.; Agostinis, P. Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. Biochim. Biophys. Acta, 2007, 1776(1), 86-107.
[PMID: 17693025]
[29]
Li, W.; Tan, G.; Cheng, J. A novel photosensitizer 31,131-phenylhydrazine -Mppa (BPHM) and its in vitro photodynamic therapy against HeLa cells. Molecules, 2016, 21(5), 558.
[http://dx.doi.org/10.3390/molecules21050558]
[30]
Bergeron, F.; Klarskov, K.; Hunting, D.J.; Wagner, J.R. Near-UV photolysis of 2-methyl-1,4-naphthoquinone-DNA duplexes: Characterization of reversible and stable interstrand cross-links between quinone and adenine moieties. Chem. Res. Toxicol., 2007, 20(5), 745-756.
[http://dx.doi.org/10.1021/tx6002968] [PMID: 17397192]
[31]
Turner, N.A.; Xia, F.; Azhar, G.; Zhang, X.; Liu, L.; Wei, J.Y. Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. J. Mol. Cell. Cardiol., 1998, 30(9), 1789-1801.
[http://dx.doi.org/10.1006/jmcc.1998.0743] [PMID: 9769235]
[32]
Jamison, J.M.; Gilloteaux, J.; Venugopal, M.; Koch, J.A.; Sowick, C.; Shah, R.; Summers, J.L. Flow cytometric and ultrastructural aspects of the synergistic antitumor activity of vitamin C-vitamin K3 combinations against human prostatic carcinoma cells. Tissue Cell, 1996, 28(6), 687-701.
[http://dx.doi.org/10.1016/S0040-8166(96)80072-3] [PMID: 9004536]
[33]
Venugopal, M.; Jamison, J.M.; Gilloteaux, J. Synergistic antitumor activity of vitamin C and K3 on human urologic tumor cell lines. Life Sci., 1996, 59(17), 1389-1400.
[34]
Ibuki, Y.; Toyooka, T.; Goto, R. Inhibition of apoptosis by menadione on exposure to UVA. Cell Biol. Toxicol., 2006, 22(5), 351-360.
[http://dx.doi.org/10.1007/s10565-006-0089-x] [PMID: 16845610]
[35]
Ridley, A.J.; Whiteside, J.R.; McMillan, T.J.; Allinson, S.L. Cellular and sub-cellular responses to UVA in relation to carcinogenesis. Int. J. Radiat. Biol., 2009, 85(3), 177-195.
[http://dx.doi.org/10.1080/09553000902740150] [PMID: 19296341]
[36]
Cadet, J.; Delatour, T.; Douki, T.; Gasparutto, D.; Pouget, J.P.; Ravanat, J.L.; Sauvaigo, S. Hydroxyl radicals and DNA base damage. Mutat. Res., 1999, 424(1-2), 9-21.
[http://dx.doi.org/10.1016/S0027-5107(99)00004-4] [PMID: 10064846]
[37]
Bracchitta, G.; Catalfo, A.; Martineau, S.; Sage, E.; De Guidi, G.; Girard, P.M. Investigation of the phototoxicity and cytotoxicity of naproxen, a non-steroidal anti-inflammatory drug, in human fibroblasts. Photochem. Photobiol. Sci., 2013, 12(5), 911-922.
[http://dx.doi.org/10.1039/c3pp25326k] [PMID: 23478633]
[38]
Cadet, J.; Wagner, J.R. DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation. Cold Spring Harb. Perspect. Biol., 2013, 5(2), 1-18.
[http://dx.doi.org/10.1101/cshperspect.a012559] [PMID: 23378590]
[39]
Castano, A.P.; Demidova, T.N.; Hamblin, M.R. Mechanisms in photodynamic therapy: Part two-cellular signaling, cell metabolism and modes of cell death. Photodiagn. Photodyn. Ther., 2005, 2(1), 1-23.
[http://dx.doi.org/10.1016/S1572-1000(05)00030-X] [PMID: 25048553]
[40]
Ding, H.; Yu, H.; Dong, Y. Photoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia. J. Control. Rel, 2011, 156(3), 276-280.
[http://dx.doi.org/10.1016/j.jconrel.2011.08.019]
[41]
Lucky, S.S.; Soo, K.C.; Zhang, Y. Nanoparticles in photodynamic therapy. Chem. Rev., 2015, 115(4), 1990-2042.
[http://dx.doi.org/10.1021/cr5004198] [PMID: 25602130]
[42]
Kwiatkowski, S.; Knap, B.; Przystupski, D.; Saczko, J.; Kędzierska, E.; Knap-Czop, K.; Kotlińska, J.; Michel, O.; Kotowski, K.; Kulbacka, J. Photodynamic therapy - mechanisms, photosensitizers and combinations. Biomed. Pharmacother., 2018, 106, 1098-1107.
[http://dx.doi.org/10.1016/j.biopha.2018.07.049] [PMID: 30119176]
[43]
Guo, W.; Sun, C.; Jiang, G.; Xin, Y. Recent developments of nanoparticles in the treatment of photodynamic therapy for cervical cancer. Anticancer. Agents Med. Chem., 2019, 19(15), 1809-1819.
[http://dx.doi.org/10.2174/1871520619666190411121953] [PMID: 30973114]
[44]
Ge, J.; Lan, M.; Zhou, B.; Liu, W.; Guo, L.; Wang, H.; Jia, Q.; Niu, G.; Huang, X.; Zhou, H.; Meng, X.; Wang, P.; Lee, C.S.; Zhang, W.; Han, X. A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation. Nat. Commun., 2014, 5, 4596.
[http://dx.doi.org/10.1038/ncomms5596] [PMID: 25105845]
[45]
Zhou, Z.; Song, J.; Nie, L.; Chen, X. Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy. Chem. Soc. Rev., 2016, 45(23), 6597-6626.
[http://dx.doi.org/10.1039/C6CS00271D] [PMID: 27722328]

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