Copyright (c) 2020 AJC
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comparative Study of Cytotoxic Activity of Nano Silver Against A549 and L929 Cell Lines
Corresponding Author(s) : R. Sharath
Asian Journal of Chemistry,
Vol. 32 No. 2 (2020): Vol 32 Issue 2
Abstract
Studies in recent years are focussed on anticancer drugs which can selectively induce cell death with less toxicity to normal cells. The present work therefore aims at exploring the potential of nano silver as selective anticancer drug by comparing its cytotoxic activity against human lung carcinoma cell line (A549) and mouse normal fibroblast cell line (L929) in vitro. Nano silver was synthesized by both chemogenic (AgNP-C) and biogenic (AgNP-B) method and characterized by using PXRD, SEM and TEM. In order to assess the molecular mechanism involved in cytotoxicity, apoptosis inducing effect of nano silver was assessed by Annexin V/PI staining, cell cycle analysis and caspase-3 expression study. From the results, it was confirmed that A549 cells treated with nano silver showed decreased cell viability (AgNP-C: 173.5 ± 2.51 μg/mL, AgNP-B: 29.2 ± 0.22 μg/mL) compared to L929 cells (AgNP-C: 317.2 ± 3.43 μg/mL, AgNP-B: 622.3 ± 1.6 μg/mL), indicating lower toxicity of nano silver towards normal cells. Apoptotic study, cell cycle analysis and caspase-3 studies showed decreased expression of Bcl-2 and increased expression of Bax mitochondrial genes facilitating release of cytochrome c (cyt c) into cytosol by disrupting mitochondrial membrane potential indicating induction of cell death in A549 cells through mitochondrial mediated intrinsic apoptosis pathway. Present investigation provides conclusive evidence for application of biogenic nano silver as a potential candidate for anticancer drug development.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- R.L. Siegel, K.D. Miller and A. Jemal, CA Cancer J. Clin., 66, 7 (2016); https://doi.org/10.3322/caac.21332.
- B.P.A. George, N. Kumar, H. Abrahamse and S.S. Ray, Sci. Rep., 8, 14368 (2018); https://doi.org/10.1038/s41598-018-32480-5.
- S. Amirsaadat, Y. Pilehvar-Soltanahmadi, F. Zarghami, S. Alipour, Z. Ebrahimnezhad and N. Zarghami, Artif. Cells Nanomed. Biotechnol., 45, 1649 (2017); https://doi.org/10.1080/21691401.2016.1276922.
- H. Mellatyar, S. Talaei, Y. Pilehvar-Soltanahmadi, M. Dadashpour, A. Barzegar, A. Akbarzadeh and N. Zarghami, Biomed. Pharmacother., 105, 1026 (2018); https://doi.org/10.1016/j.biopha.2018.06.083.
- R. Govender, A. Phulukdaree, R.M. Gengan, K. Anand and A.A. Chuturgoon, J. Nanobiotechnology, 11, 5 (2013); https://doi.org/10.1186/1477-3155-11-5.
- M. Dadashpour, A. Firouzi-Amandi, M. Pourhassan-Moghaddam, M.J. Maleki, N. Soozangar, F. Jeddi, M. Nouri, N. Zarghami and Y. PilehvarSoltanahmadi, Mater. Sci. Eng. C, 92, 902 (2018); https://doi.org/10.1016/j.msec.2018.07.053.
- M.E. Davis, Z. Chen and D.M. Shin, Nat. Rev. Drug Discov., 7, 771 (2008); https://doi.org/10.1038/nrd2614.
- K. Cho, X. Wang, S. Nie, Z. Chen and D.M. Shin, Clin. Cancer Res., 14, 1310 (2008); https://doi.org/10.1158/1078-0432.CCR-07-1441.
- C.G. Kim, V. Castro-Aceituno, R. Abbai, H.A. Lee, S.Y. Simu, Y. Han, J. Hurh, Y.J. Kim and D.C. Yang, Biomed. Pharmacother., 99, 128 (2018); https://doi.org/10.1016/j.biopha.2018.01.050.
- S. Gurunathan, J.H. Park, J.W. Han and J.H. Kim, Int. J. Nanomedicine, 10, 4203 (2015); https://doi.org/10.2147/IJN.S83953.
- W.R. Li, X.B. Xie, Q.S. Shi, H.Y. Zeng, Y.S. Ou-Yang and Y.B. Chen, Appl. Microbiol. Biotechnol., 85, 1115 (2010); https://doi.org/10.1007/s00253-009-2159-5.
- P. Mukherjee, A. Ahmad, D. Mandal, S. Senapati, S.R. Sainkar, M.I. Khan, R. Parishcha, P.V. Ajaykumar, M. Alam, R. Kumar and M. Sastry, Nano Lett., 1, 515 (2001); https://doi.org/10.1021/nl0155274.
- K. Samrat, N.S. Nikhil, S. Karthick Raja Namasivamyam, R. Sharath, M.N. Chandraprabha, B.G. Harish, H. Muktha and R.G. Kashyap, Mater. Today Proc., 3, 1958 (2016); https://doi.org/10.1016/j.matpr.2016.04.097.
- S. Chernousova and M. Epple, Angew. Chem. Int. Ed., 52, 1636 (2013); https://doi.org/10.1002/anie.201205923.
- X.F. Zhang, Z.G. Liu, W. Shen and S. Gurunathan, Int. J. Mol. Sci., 17, 1534 (2016); https://doi.org/10.3390/ijms17091534.
- A.K. Pujashree, A. Rajeshwari, M.N. Chandraprabha and A. Mukherjee, J. Nanosci. Nanoeng. Appl., 4, 33 (2014).
- A.-C. Burdusel, O. Gherasim, A.M. Grumezescu, L. Mogoanta, A. Ficai and E. Andronescu, Nanomaterials, 8, 681 (2018); https://doi.org/10.3390/nano8090681.
- Y. He, Z. Du, S. Ma, Y. Liu, D. Li, H. Huang, S. Jiang, S. Cheng, W. Wu, K. Zhang and X. Zheng, Int. J. anomedicine, 11, 1879 (2016); https://doi.org/10.2147/IJN.S103695.
- S. Annu, S. Ahmed, G. Kaur, P. Sharma, S. Singh and S. Ikram, Toxicol. Res., 7, 923 (2018); https://doi.org/10.1039/C8TX00103K.
- D.R. Nogueira, C.M.B. Rolim and A.A. Farooqi, Asian Pac. J. Cancer Prev., 15, 4739 (2014); https://doi.org/10.7314/APJCP.2014.15.12.4739.
- V. Castro-Aceituno, S. Ahn, S.Y. Simu, P. Singh, R. Mathiyalagan, H.A. Lee and D.C. Yang, Biomed. Pharmacother., 84, 158 (2016); https://doi.org/10.1016/j.biopha.2016.09.016.
- P. Durai, A. Chinnasamy, B. Gajendran, M. Ramar, S. Pappu, G. Kasivelu and A. Thirunavukkarasu, Eur. J. Med. Chem., 84, 90 (2014); https://doi.org/10.1016/j.ejmech.2014.07.012.
- V. Kumar and S.K. Yadav, J. Chem. Technol. Biotechnol., 84, 151 (2009); https://doi.org/10.1002/jctb.2023.
- U.K. Parashar, P.S. Sexena and S. Anchal, Dig. J. Nanomater. Biostruct.,4, 159 (2009).
- M.N. Alam, N. Roy, D. Mandal and N.A. Begum, RSC Adv., 3, 11935 (2013); https://doi.org/10.1039/c3ra23133j.
- N. Kanipandian, D. Li and S. Kannan, Biotechnol. Rep., 23, e00339 (2019); https://doi.org/10.1016/j.btre.2019.e00339.
- S. Zafar and A. Zafar, Open Biotechnol. J., 13, 37 (2019); https://doi.org/10.2174/1874070701913010037.
- S. Annu, S. Ahmed, G. Kaur, P. Sharma, S. Singh and S. Ikram, J. Appl. Biomed., 16, 221 (2018); https://doi.org/10.1016/j.jab.2018.02.002.
- S. Devanesan, M.S. AlSalhi, R.V. Balaji, A.J.A. Ranjitsingh, A. Ahamed, A.A. Alfuraydi, F.Y. AlQahtani, F.S. Aleanizy and A.H. Othman, Nanoscale Res. Lett., 13, 315 (2018); https://doi.org/10.1186/s11671-018-2731-y.
- T. Kokila, P.S. Ramesh and D. Geetha, Appl. Nanosci., 5, 911 (2015); https://doi.org/10.1007/s13204-015-0401-2.
- R.S.A. Bharani and S.K.R. Namasivayam, J. Environ. Chem. Eng., 5, 453 (2017); https://doi.org/10.1016/j.jece.2016.12.023.
- S. Agnihotri, S. Mukherji and S.S. Mukherji, RSC Adv., 4, 3974 (2014); https://doi.org/10.1039/C3RA44507K.
- M.N. Nadagouda, N. Iyanna, J. Lalley, C. Han, D.D. Dionysiou and R.S. Varma, ACS Sustain. Chem. Eng., 2, 1717 (2014); https://doi.org/10.1021/sc500237k.
- P. Chairuangkitti, S. Lawanprasert, S. Roytrakul, S. Aueviriyavit, D. Phummiratch, K. Kulthong, P. Chanvorachote and R. Maniratanachote, Toxicol. In Vitro, 27, 330 (2013); https://doi.org/10.1016/j.tiv.2012.08.021.
- H. Yang, Y. Ren, T. Wang and C. Wang, Results in Phys., 6, 299 (2016); https://doi.org/10.1016/j.rinp.2016.05.012.
- M. Jeyaraj, G. Sathishkumar, G. Sivanandhan, D. MubarakAli, M. Rajesh, R. Arun, G. Kapildev, M. Manickavasagam, N. Thajuddin, K. Premkumar and A. Ganapathi, Colloids Surf. B Biointerfaces, 106, 86 (2013); https://doi.org/10.1016/j.colsurfb.2013.01.027.
- P. Sanpui, A. Chattopadhyay and S.S. Ghosh, ACS Appl. Mater. Interfaces, 3, 218 (2011); https://doi.org/10.1021/am100840c.
- M. Jeyaraj, M. Rajesh, R. Arun, D. MubarakAli, G. Sathishkumar, G.K. Dev, G. Sivanandhan, M. Manickavasagam, K. Premkumar, N. Thajuddin and A. Ganapathi, Colloids Surf. B Biointerfaces, 102, 708 (2013); https://doi.org/10.1016/j.colsurfb.2012.09.042.
- R.M. Gengan, K. Anand, A. Phulukdaree and A. Chuturgoon, Colloids Surf. B Biointerfaces, 105, 87 (2013); https://doi.org/10.1016/j.colsurfb.2012.12.044.
- Y.S. Lee, D.W. Kim, Y.H. Lee, J.H. Oh, S. Yoon, M.S. Choi, S.K. Lee, J.W. Kim, K. Lee and C.W. Song, Arch. Toxicol., 85, 1529 (2011); https://doi.org/10.1007/s00204-011-0714-1.
- M.I. Sriram, S.B. Kanth, K. Kalishwaralal and S. Gurunathan, Int. J. Nanomedicine, 5, 753 (2010); https://doi.org/10.2147/IJN.S11727.
- V. De Matteis, M.A. Malvindi, A. Galeone, V. Brunetti, E. De Luca, S. Kote, P. Kshirsagar, S. Sabella, G. Bardi and P.P. Pompa, Nanomedicine, 11, 731 (2015); https://doi.org/10.1016/j.nano.2014.11.002.
- J.L. Fang and F.A. Beland, Toxicol. Sci., 111, 120 (2009); https://doi.org/10.1093/toxsci/kfp136.
- L. Zhang, J. Zhang, C.Q. Hu, J. Cao, X.L. Zhou, Y.Z. Hu, Q.J. He and B. Yang, Anticancer Drugs, 20, 416 (2009); https://doi.org/10.1097/CAD.0b013e32832aa7b0.
- A.K. Sekone, Y.-B. Chen, M.-C. Lu, W.-K. Chen, C.-A. Liu and M.-T. Lee, Nanoscale Res. Lett., 11, 1 (2016); https://doi.org/10.1186/s11671-015-1209-4.
- A. De Martino, G. Filomeni, K. Aquilano, M.R. Ciriolo and G. Rotilio, J. Nutr. Biochem., 17, 742 (2006); https://doi.org/10.1016/j.jnutbio.2005.12.005.
- P.V. AshaRani, G.L.K. Mun, M.P. Hande and S. Valiyaveettil, ACS Nano, 3, 279 (2009); https://doi.org/10.1021/nn800596w.
- C.F. Gao, S. Ren, L. Zhang, T. Nakajima, S. Ichinose, T. Hara, K. Koike and N. Tsuchida, Exp. Cell Res., 265, 145 (2001); https://doi.org/10.1006/excr.2001.5171.
- J. Cai, J. Yang and D.P. Jones, Biochim. Biophys. Acta, 1366, 139 (1998); https://doi.org/10.1016/S0005-2728(98)00109-1.
References
R.L. Siegel, K.D. Miller and A. Jemal, CA Cancer J. Clin., 66, 7 (2016); https://doi.org/10.3322/caac.21332.
B.P.A. George, N. Kumar, H. Abrahamse and S.S. Ray, Sci. Rep., 8, 14368 (2018); https://doi.org/10.1038/s41598-018-32480-5.
S. Amirsaadat, Y. Pilehvar-Soltanahmadi, F. Zarghami, S. Alipour, Z. Ebrahimnezhad and N. Zarghami, Artif. Cells Nanomed. Biotechnol., 45, 1649 (2017); https://doi.org/10.1080/21691401.2016.1276922.
H. Mellatyar, S. Talaei, Y. Pilehvar-Soltanahmadi, M. Dadashpour, A. Barzegar, A. Akbarzadeh and N. Zarghami, Biomed. Pharmacother., 105, 1026 (2018); https://doi.org/10.1016/j.biopha.2018.06.083.
R. Govender, A. Phulukdaree, R.M. Gengan, K. Anand and A.A. Chuturgoon, J. Nanobiotechnology, 11, 5 (2013); https://doi.org/10.1186/1477-3155-11-5.
M. Dadashpour, A. Firouzi-Amandi, M. Pourhassan-Moghaddam, M.J. Maleki, N. Soozangar, F. Jeddi, M. Nouri, N. Zarghami and Y. PilehvarSoltanahmadi, Mater. Sci. Eng. C, 92, 902 (2018); https://doi.org/10.1016/j.msec.2018.07.053.
M.E. Davis, Z. Chen and D.M. Shin, Nat. Rev. Drug Discov., 7, 771 (2008); https://doi.org/10.1038/nrd2614.
K. Cho, X. Wang, S. Nie, Z. Chen and D.M. Shin, Clin. Cancer Res., 14, 1310 (2008); https://doi.org/10.1158/1078-0432.CCR-07-1441.
C.G. Kim, V. Castro-Aceituno, R. Abbai, H.A. Lee, S.Y. Simu, Y. Han, J. Hurh, Y.J. Kim and D.C. Yang, Biomed. Pharmacother., 99, 128 (2018); https://doi.org/10.1016/j.biopha.2018.01.050.
S. Gurunathan, J.H. Park, J.W. Han and J.H. Kim, Int. J. Nanomedicine, 10, 4203 (2015); https://doi.org/10.2147/IJN.S83953.
W.R. Li, X.B. Xie, Q.S. Shi, H.Y. Zeng, Y.S. Ou-Yang and Y.B. Chen, Appl. Microbiol. Biotechnol., 85, 1115 (2010); https://doi.org/10.1007/s00253-009-2159-5.
P. Mukherjee, A. Ahmad, D. Mandal, S. Senapati, S.R. Sainkar, M.I. Khan, R. Parishcha, P.V. Ajaykumar, M. Alam, R. Kumar and M. Sastry, Nano Lett., 1, 515 (2001); https://doi.org/10.1021/nl0155274.
K. Samrat, N.S. Nikhil, S. Karthick Raja Namasivamyam, R. Sharath, M.N. Chandraprabha, B.G. Harish, H. Muktha and R.G. Kashyap, Mater. Today Proc., 3, 1958 (2016); https://doi.org/10.1016/j.matpr.2016.04.097.
S. Chernousova and M. Epple, Angew. Chem. Int. Ed., 52, 1636 (2013); https://doi.org/10.1002/anie.201205923.
X.F. Zhang, Z.G. Liu, W. Shen and S. Gurunathan, Int. J. Mol. Sci., 17, 1534 (2016); https://doi.org/10.3390/ijms17091534.
A.K. Pujashree, A. Rajeshwari, M.N. Chandraprabha and A. Mukherjee, J. Nanosci. Nanoeng. Appl., 4, 33 (2014).
A.-C. Burdusel, O. Gherasim, A.M. Grumezescu, L. Mogoanta, A. Ficai and E. Andronescu, Nanomaterials, 8, 681 (2018); https://doi.org/10.3390/nano8090681.
Y. He, Z. Du, S. Ma, Y. Liu, D. Li, H. Huang, S. Jiang, S. Cheng, W. Wu, K. Zhang and X. Zheng, Int. J. anomedicine, 11, 1879 (2016); https://doi.org/10.2147/IJN.S103695.
S. Annu, S. Ahmed, G. Kaur, P. Sharma, S. Singh and S. Ikram, Toxicol. Res., 7, 923 (2018); https://doi.org/10.1039/C8TX00103K.
D.R. Nogueira, C.M.B. Rolim and A.A. Farooqi, Asian Pac. J. Cancer Prev., 15, 4739 (2014); https://doi.org/10.7314/APJCP.2014.15.12.4739.
V. Castro-Aceituno, S. Ahn, S.Y. Simu, P. Singh, R. Mathiyalagan, H.A. Lee and D.C. Yang, Biomed. Pharmacother., 84, 158 (2016); https://doi.org/10.1016/j.biopha.2016.09.016.
P. Durai, A. Chinnasamy, B. Gajendran, M. Ramar, S. Pappu, G. Kasivelu and A. Thirunavukkarasu, Eur. J. Med. Chem., 84, 90 (2014); https://doi.org/10.1016/j.ejmech.2014.07.012.
V. Kumar and S.K. Yadav, J. Chem. Technol. Biotechnol., 84, 151 (2009); https://doi.org/10.1002/jctb.2023.
U.K. Parashar, P.S. Sexena and S. Anchal, Dig. J. Nanomater. Biostruct.,4, 159 (2009).
M.N. Alam, N. Roy, D. Mandal and N.A. Begum, RSC Adv., 3, 11935 (2013); https://doi.org/10.1039/c3ra23133j.
N. Kanipandian, D. Li and S. Kannan, Biotechnol. Rep., 23, e00339 (2019); https://doi.org/10.1016/j.btre.2019.e00339.
S. Zafar and A. Zafar, Open Biotechnol. J., 13, 37 (2019); https://doi.org/10.2174/1874070701913010037.
S. Annu, S. Ahmed, G. Kaur, P. Sharma, S. Singh and S. Ikram, J. Appl. Biomed., 16, 221 (2018); https://doi.org/10.1016/j.jab.2018.02.002.
S. Devanesan, M.S. AlSalhi, R.V. Balaji, A.J.A. Ranjitsingh, A. Ahamed, A.A. Alfuraydi, F.Y. AlQahtani, F.S. Aleanizy and A.H. Othman, Nanoscale Res. Lett., 13, 315 (2018); https://doi.org/10.1186/s11671-018-2731-y.
T. Kokila, P.S. Ramesh and D. Geetha, Appl. Nanosci., 5, 911 (2015); https://doi.org/10.1007/s13204-015-0401-2.
R.S.A. Bharani and S.K.R. Namasivayam, J. Environ. Chem. Eng., 5, 453 (2017); https://doi.org/10.1016/j.jece.2016.12.023.
S. Agnihotri, S. Mukherji and S.S. Mukherji, RSC Adv., 4, 3974 (2014); https://doi.org/10.1039/C3RA44507K.
M.N. Nadagouda, N. Iyanna, J. Lalley, C. Han, D.D. Dionysiou and R.S. Varma, ACS Sustain. Chem. Eng., 2, 1717 (2014); https://doi.org/10.1021/sc500237k.
P. Chairuangkitti, S. Lawanprasert, S. Roytrakul, S. Aueviriyavit, D. Phummiratch, K. Kulthong, P. Chanvorachote and R. Maniratanachote, Toxicol. In Vitro, 27, 330 (2013); https://doi.org/10.1016/j.tiv.2012.08.021.
H. Yang, Y. Ren, T. Wang and C. Wang, Results in Phys., 6, 299 (2016); https://doi.org/10.1016/j.rinp.2016.05.012.
M. Jeyaraj, G. Sathishkumar, G. Sivanandhan, D. MubarakAli, M. Rajesh, R. Arun, G. Kapildev, M. Manickavasagam, N. Thajuddin, K. Premkumar and A. Ganapathi, Colloids Surf. B Biointerfaces, 106, 86 (2013); https://doi.org/10.1016/j.colsurfb.2013.01.027.
P. Sanpui, A. Chattopadhyay and S.S. Ghosh, ACS Appl. Mater. Interfaces, 3, 218 (2011); https://doi.org/10.1021/am100840c.
M. Jeyaraj, M. Rajesh, R. Arun, D. MubarakAli, G. Sathishkumar, G.K. Dev, G. Sivanandhan, M. Manickavasagam, K. Premkumar, N. Thajuddin and A. Ganapathi, Colloids Surf. B Biointerfaces, 102, 708 (2013); https://doi.org/10.1016/j.colsurfb.2012.09.042.
R.M. Gengan, K. Anand, A. Phulukdaree and A. Chuturgoon, Colloids Surf. B Biointerfaces, 105, 87 (2013); https://doi.org/10.1016/j.colsurfb.2012.12.044.
Y.S. Lee, D.W. Kim, Y.H. Lee, J.H. Oh, S. Yoon, M.S. Choi, S.K. Lee, J.W. Kim, K. Lee and C.W. Song, Arch. Toxicol., 85, 1529 (2011); https://doi.org/10.1007/s00204-011-0714-1.
M.I. Sriram, S.B. Kanth, K. Kalishwaralal and S. Gurunathan, Int. J. Nanomedicine, 5, 753 (2010); https://doi.org/10.2147/IJN.S11727.
V. De Matteis, M.A. Malvindi, A. Galeone, V. Brunetti, E. De Luca, S. Kote, P. Kshirsagar, S. Sabella, G. Bardi and P.P. Pompa, Nanomedicine, 11, 731 (2015); https://doi.org/10.1016/j.nano.2014.11.002.
J.L. Fang and F.A. Beland, Toxicol. Sci., 111, 120 (2009); https://doi.org/10.1093/toxsci/kfp136.
L. Zhang, J. Zhang, C.Q. Hu, J. Cao, X.L. Zhou, Y.Z. Hu, Q.J. He and B. Yang, Anticancer Drugs, 20, 416 (2009); https://doi.org/10.1097/CAD.0b013e32832aa7b0.
A.K. Sekone, Y.-B. Chen, M.-C. Lu, W.-K. Chen, C.-A. Liu and M.-T. Lee, Nanoscale Res. Lett., 11, 1 (2016); https://doi.org/10.1186/s11671-015-1209-4.
A. De Martino, G. Filomeni, K. Aquilano, M.R. Ciriolo and G. Rotilio, J. Nutr. Biochem., 17, 742 (2006); https://doi.org/10.1016/j.jnutbio.2005.12.005.
P.V. AshaRani, G.L.K. Mun, M.P. Hande and S. Valiyaveettil, ACS Nano, 3, 279 (2009); https://doi.org/10.1021/nn800596w.
C.F. Gao, S. Ren, L. Zhang, T. Nakajima, S. Ichinose, T. Hara, K. Koike and N. Tsuchida, Exp. Cell Res., 265, 145 (2001); https://doi.org/10.1006/excr.2001.5171.
J. Cai, J. Yang and D.P. Jones, Biochim. Biophys. Acta, 1366, 139 (1998); https://doi.org/10.1016/S0005-2728(98)00109-1.