The photocytotoxicity effect of cationic sulfonated corrole towards lung cancer cells: in vitro and in vivo study

Abstract

Corrole is a kind of new and promising photosensitizer (PS) in cancer photodynamic therapy (PDT). However, the protein molecular mechanism of PDT activity for corrole under light irradiation is still not clear. In this paper, water-soluble cationic sulfonated corrole (1) and its metal complexes (1-Fe, 1-Mn, and 1-Cu) were prepared, and the photodynamic anti-cancer activity against various tumor cells was investigated by MTT assay. The potential molecular mechanism of PDT activity was elucidated by fluorescence microscope, flow cytometry, molecular docking, and western blotting analysis. Besides, the potential PDT anti-tumor effect of 1 in vivo was assessed in human tumor xenografts in mice. Quantitative analysis revealed that 1’s phototoxicity triggered a significant generation of reactive oxygen species, causing disruption of mitochondrial membrane potential. The results of western blotting (WB) assay shown in 1’s phototoxicity could induce cell apoptosis via ROS-mediated mitochondrial caspase apoptosis pathway, in which SIRT1 protein degradation played a key role. PTD activity in vivo shown in 1 could significantly reduce the growth of A549 xenografted tumor, without obvious loss of mice body weight. We clearly found that cationic sulfonated corrole is a potential candidate of PS in vitro and in vivo. The phototoxicity of 1 could induce A549 cell apoptosis by inducing ROS production increase, further to activate the mitochondrial apoptosis pathway. We concluded that SIRT1 protein is a more appropriate target in this progress.

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References

  1. 1.

    Paolesse R (2000) In: Kadish KM, Smith KM, Guilard R (eds) Porphyrin Handbook, Vol. 2. Academic Press, San Diego, pp 201–232

    Google Scholar 

  2. 2.

    Liu HY, Lai TS, Yeung LL, Chang CK (2003) First synthesis of perfluorinated corrole and its Mn=O complex. Org Lett 5(5):617–620

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Fu BQ, Huang J, Ren L, Weng XC, Zhou YY, Du YH, Wu XJ, Zhou X, Yang GF (2007) Cationic corrole derivatives: a new family of G-quadruplex inducing and stabilizing ligands. Chem Commun 0(31):3264–3266. https://doi.org/10.1039/B704599A

    CAS  Article  Google Scholar 

  4. 4.

    Mahammed A, Gross Z (2017) Corroles as triplet photosensitizers. Coord Chem Rev. https://doi.org/10.1016/j.ccr.2017.08.028

  5. 5.

    Fu BQ, Zhang D, Weng XC et al (2008) Cationic metal-corrole complexes: design, synthesis, and properties of guanine-quadruplex stabilizers. Chem Eur J 14(30):9431–9441

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Zou HB, Yang H, Liu ZL et al (2015) Iron(IV)-corrole catalyzed stereoselective olefination of aldehydes with ethyl diazoacetate. Organometn 34(12):2791–2795

    CAS  Article  Google Scholar 

  7. 7.

    Preuß A, Saltsman I, Mahammed A et al (2014) Photodynamic inactivation of mold fungi spores by newly developed charged corroles. J Photochem Photobiol B 133(5):39–46

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Okun Z, Kupershmidt L, Amit T et al (2009) Manganese corroles prevent intracellular nitration and subsequent death of insulin-producing cells. ACS Chem Biol 4(11):910–914

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Haber A, Mahammed A, Fuhrman B et al (2008) Amphiphilic/bipolar metallocorroles that catalyze the decomposition of reactive oxygen and nitrogen species, rescue lipoproteins from oxidative damage, and attenuate atherosclerosis in mice. Angew Chem Int Ed 47(41):7896–7900

    CAS  Article  Google Scholar 

  10. 10.

    Teo RD, Hwang YY, Termini J, Gross Z, Gray HB (2017) Fighting cancer with corroles. Chem Rev 117(4):2711–2729

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Gross Z, Mahammed A, Abdales M, Weaver JJ, Gray HB (2003) Bioinorganic chemistry of corrole metal complexes: interactions with proteins and cells. J Inorg Biochem 96(1):140

    Article  Google Scholar 

  12. 12.

    Lim P, Mahammed A, Okun Z et al (2012) Differential cytostatic and cytotoxic action of metallocorroles against human cancer cells: potential platforms for anticancer drug development. Chem Res Toxicol 25(2):400–409

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Agadjanian H, Weaver JJ, Mahammed A et al (2006) Specific delivery of corroles to cells via noncovalent conjugates with viral proteins. Pharm Res 23(2):367–377

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Agadjanian H, Ma J, Rentsendorj A et al (2009) Tumor detection and elimination by a targeted gallium corrole. PNAS 106(15):6105–6110

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Hwang JY, Lubow J, Chu D, Ma J, Agadjanian H et al (2011) A mechanistic study of tumor-targeted corrole toxicity. Mol Pharm 8(6):2233–2243

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Aviv-Harel I, Gross Z (2011) Coordination chemistry of corroles with focus on main group elements. Coord Chem Rev 255(7–8):717–736

    CAS  Article  Google Scholar 

  17. 17.

    Chang CK, Kong P, Liu HY et al (2006) Synthesis and photodynamic activities of modified corrole derivatives on nasopharyngeal carcinoma cells. Proc SPIE, SPIE: Bellingham WA USA 6139:268–278. https://doi.org/10.1117/12.646328

    CAS  Article  Google Scholar 

  18. 18.

    Hwang JY, Lubow DJ, Chu D et al (2012) Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity. J Control Release 163(3):368–373

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Sims JD, Hwang JY, Wagner S et al (2015) A corrole nanobiologic elicitstissue-activated MRI contrast enhancement and tumor-targeted toxicity. J Control Release 217(10):92–101

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Barata JFB, Zamarrón A, Neves MGPMS et al (2015) Photodynamic effects induced by meso-tris(pentafluorophenyl)corrole and its cyclodextrin conjugates on cytoskeletal components of HeLa cells. Eur J Med Chem 92(6):135–144

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Liang ZH, Liu HY, Zhou R et al (2016) DNA-binding, photocleavage, and photodynamic anti-cancer activities of pyridyl corroles. J Membr Biol 249(4):419–428

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Wang YG, Zhang Z, Wang H, Liu HY (2016) Phosphorus(V) corrole: DNA binding, photonuclease activity and cytotoxicity toward tumor cells. Bioorg Chem 67:57–63

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Liang ZH, Liu HY, Jiang GB, Wen JY, Liu YJ, Xiao XY (2016) Polyhydric corrole and its gallium complex: synthesis, DNA-binding properties and photodynamic activities. Chin J Chem 34(10):997–1005

    CAS  Article  Google Scholar 

  24. 24.

    Shi L, Yang WC, Zeng SY et al (2016) DNA-binding and anti-tumor activities of cobalt corrole complexes. Chem J Chin Univ 37(6):1059–1068. https://doi.org/10.7503/cjcu20160029

    CAS  Article  Google Scholar 

  25. 25.

    Cheng F, Huang LT, Wang HH et al (2017) Photodynamic therapy activities of 10-(4-formylphenyl)-5,15-bis(pentafluorophenyl)corrole and its gallium complex. Chin J Chem 35(1):86–92

    CAS  Article  Google Scholar 

  26. 26.

    Zhang Z, Wang HH, Yu HJ et al (2017) Synthesis, characterization and in vitro and in vivo photodynamic activities of a gallium(III) tris(ethoxycarbonyl)corrole. Dalton Trans 46(29):9481–9490

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Zhang Z, Wen JY, Lv BB et al (2016) Photocytotoxicity and G-quadruplex DNA interaction of water-soluble gallium(III) tris (N-methyl-4-pyridyl)corrole complex. Appl Organomet Chem 30(3):132–139

    CAS  Article  Google Scholar 

  28. 28.

    Zhang Y, Wen JY, Wang XL et al (2014) DNA binding and nuclease activity of cationic iron(IV) and manganese(III) corrole complexes. Appl Organomet Chem 28(7):559–566

    CAS  Article  Google Scholar 

  29. 29.

    Na N, Zhao DQ, Li H, Jiang N, Wen JY, Liu HY (2016) DNA binding, photonuclease activity and human serum albumin interaction of a water-soluble freebase carboxyl corrole. Molecules 21(1):1–14. https://doi.org/10.3390/molecules21010054

    CAS  Article  Google Scholar 

  30. 30.

    Zhang Y, Wang Q, Wen JY et al (2013) DNA binding and oxidative cleavage by a water-soluble carboxyl manganese(III) corrole. Chin J Chem 31(10):1321–1328

    CAS  Article  Google Scholar 

  31. 31.

    Lu J, Liu HY, Shi L et al (2011) DNA cleavage mediated by water-soluble manganese corrole. Chin Chem Lett 22(1):101–104

    CAS  Article  Google Scholar 

  32. 32.

    Zhang Y, Wen JY, Mahmood MHR, Wang XL, Lv BB, Ying X, Wang H, Ji LN, Liu HY (2015) DNA/HSA interaction and nuclease activity of an iron(III) amphiphilic sulfonated corrole. Luminescence 30(7):1045–1054

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Huang JT, Wang XL, Zhang Y et al (2013) DNA binding and nuclease activity of a water-soluble sulfonated manganese(III) corrole. Transit Met Chem 38(3):283–289

    CAS  Article  Google Scholar 

  34. 34.

    Zhang HT, Wu J, Wen M, Su LJ, Luo H (2012) Galangin induces apoptosis in hepatocellular carcinoma cells through the caspase 8/t-bid mitochondrial pathway. J Asian Nat Prod Res 14(7):626–633

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Zhang HT, Li N, Wu J, Su LJ, Chen XY, Lin BY, Luo H (2013) Galangin inhibits proliferation of HepG2 cells by activating AMPK via increasing the AMP/TAN ratio in a LKB1-independent manner. Eur J Pharmacol 718(1–3):235–244

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Lucky SS, Soo KC, Zhang Y (2015) Nanoparticles in photodynamic therapy. Chem Rev 115(4):1990–2042

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Ethirajan M, Chen YH, Joshi P, Pandey RK (2011) The role of porphyrin chemistry in tumor imaging and photodynamic therapy. Chem Soc Rev 40(1):340–362

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Calixto GMF, Bernegossi J, Freitas LM, Fontana CR, Chorilli M (2016) Nanotechnology-based drug delivery systems for photodynamic therapy of cancer: a review. Molecules 21(3):342

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  39. 39.

    Jeon S, Wang M, Tan LS, Cooper T, Hamblin MR, Chiang LY (2013) Synthesis of photoresponsive dual NIR two-photon absorptive [60]fullerene triads and tetrads. Molecules 18(8):9603–9622

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Xia CH, Wang Y, Chen W, Yu WX, Wang BQ, Li T (2011) New hydrophilic /lipophilic tetra-α-(4-carboxyphenoxy) phthalocyanine zinc-mediated photodynamic therapy inhibits the proliferation of human hepatocellular carcinoma Bel-7402 cells by triggering apoptosis and arresting cell cycle. Molecules 16(2):1389–1401

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Simone BCD, Mazzone G, Russo N, Sicilia E, Toscano M (2017) Metal atom effect on the photophysical properties of Mg(II), Zn(II), Cd(II), and Pd(II) tetraphenylporphyrin complexes proposed as possible drugs in photodynamic therapy. Molecules 22(7):1093

    PubMed Central  Article  CAS  Google Scholar 

  42. 42.

    Rodriguez ME, Zhang P, Azizuddin K et al (2009) Structural factors and mechanisms underlying the improved photodynamic cell killing with silicon phthalocyanine photosensitizers directed to lysosomes versus mitochondria. Photochem Photobiol 85(5):1189–1200

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Wang H, Zheng JH, Xu WJ et al (2017) A new series of cytotoxic pyrazoline derivatives as potential anticancer agents that induce cell cycle arrest and apoptosis. Molecules 22(10):1635

    PubMed Central  Article  CAS  Google Scholar 

  44. 44.

    Miniotis MF, Mukwaya A, Wingren AG (2014) Digital holographic microscopy for non-invasive monitoring of cell cycle arrest in L929 cells. PLoS One 9(9):e106546

    Article  CAS  Google Scholar 

  45. 45.

    Meschini S, Pellegrini E, Condello M, Occhionero G, Delfine S, Condello G, Mastrodonato F (2017) Cytotoxic and apoptotic activities of prunus spinosa trigno ecotype extract on human cancer cells. Molecules 22(10):157. https://doi.org/10.3390/molecules22091578

    CAS  Article  Google Scholar 

  46. 46.

    Rasul A, Bao R, Malhi M, Zhao B, Tsuji I, Li J, Li XM (2013) Induction of apoptosis by costunolide in bladder cancer cells is mediated through ROS generation and mitochondrial dysfunction. Molecules 18(2):1418–1433

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Kankala RK, Tsai PY, Kuthati Y, Wei PR, Liu CL, Lee CH (2017) Overcoming multidrug resistance through co-delivery of ROS-generating nano-machinery in cancer therapeutics. J Mater Chem B 5(7):1507–1517

    CAS  Article  Google Scholar 

  48. 48.

    Kankala RK, Kuthati Y, Liu CL, Lee CH (2015) Hierarchical coated metal hydroxide nanoconstructs as potential controlled release carriers of photosensitizer for skin melanoma. RSC Adv 5(53):42666–42680

    CAS  Article  Google Scholar 

  49. 49.

    Kankala RK, Liu CG, Chen AZ et al (2017) Overcoming multidrug resistance through the synergistic effects of hierarchical pH-sensitive, ROS-generating nanoreactors. ACS Biomater-SCI Eng 3(10):2431–2442

    CAS  Article  Google Scholar 

  50. 50.

    Shukla S, Sharma A, Pandey VK, Raisuddin S, Kakkar P (2016) Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells. Toxicol Appl Pharmacol 291(15):70–83

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Suzuki M, Bandoski C, Bartlett JD (2015) Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling. Free Radic Biol Med 89:369–378

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Kessel D, Vicente MGH, Jr JJR (2006) Initiation of apoptosis and autophagy by photodynamic therapy. Lasers Surg Med 38(5):482–488

    PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Li X, Wang YJ, Xiong YZ, Wu J, Ding H, Chen XY, Lan LB, Zhang HT (2016) Galangin induces autophagy via deacetylation of LC3 by SIRT1 in HepG2 cells. Sci Report 07(6):30496

    Article  CAS  Google Scholar 

  54. 54.

    Oberdoerffer P, Michan S, Mcvay M et al (2008) SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell 135(5):907–918

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Panta K, Yadava AK, Guptaa P, Islama R, Sarayab A, Venugopal SK (2017) Butyrate induces ROS-mediated apoptosis by modulating miR-22/SIRT-1 pathway in hepatic cancer cells. Redox Biol 12:340–349

    Article  CAS  Google Scholar 

  56. 56.

    Reiners JJ Jr, Caruso JA, Mathieu P, Chelladurai B, Yin XM, Kessel D (2002) Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage. Cell Death Differ 9(9):934–944

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Kessel D, Jr JJR (2017) Effects of combined lysosomal and mitochondrial photodamage in a non-small-cell lung cancer cell line: the role of paraptosis. Photochem Photobiol 93(6):1502–1508

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. 58.

    Whitacre CM, Satoh TH, Xue LY, Gordon NH, Oleinick NL (2002) Photodynamic therapy of human breast cancer xenografts lacking caspase-3. Cancer Lett 179(1):43–49

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Idris NM, Gnanasammandhan MK, Zhang J, Ho PC, Mahendran R, Zhang Y (2012) In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nat Med 18(10):1580–1585

    CAS  PubMed  Article  Google Scholar 

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Funding

This work is financially supported by National Natural Science Foundation of China (NNSFC) (Nos. 21671068, 81772634), Postdoctoral Initial Foundation of Guangdong Medical University (No. BH08073), Science Foundation of Guangdong Medical University (No. 2001/2XK16042), and Science Foundation of Zhanjiang (2017B01064).

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Correspondence to Hai-Yang Liu or Hai-Tao Zhang.

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All procedures performed in studies involving animal participants were in accordance with the ethical standards of the institutional and/or national research committee. Animal experiments were performed in accordance with protocols approved by the institutional ethics committee of Guangdong Medical University (ID Number GDY1702014), and the detailed information can be found in the suggestion of animal research ethics.

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Zhang, Z., Yu, H., Huang, H. et al. The photocytotoxicity effect of cationic sulfonated corrole towards lung cancer cells: in vitro and in vivo study. Lasers Med Sci 34, 1353–1363 (2019). https://doi.org/10.1007/s10103-019-02725-4

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Keywords

  • Corrole
  • Photocytotoxicity
  • ROS-mediated
  • SIRT1