Vanadium oxide 3- methoxy salen, a synthetic biologically active complex against cancerous cell lines
,
Abstract
Background: Vanadium is an essential dietary microelement that plays a key role in the metabolic pathways and has anti-neoplastic effects. In this regard, vanadium oxide 3-methoxy salen complex was produced and its anticancer effects were evaluated. Methods: Schiff bases produced from equivamounts of Vanadyl acetylacetonate [VO(acac)2] in methanol were used to make a vanadium oxide 3-methoxy salen complex. Then, antioxidant property of compound, cell viability and cytotoxicity assay, DNA fragmentation analysis and determination of the apoptosis pathway genes were evaluated. Results: Result showed that compound with an RC50 value of 126.3 µM, the compound demonstrated considerable free radical scavenging activity. The combination strongly suppressed the viability and proliferation of HeLa and McCoy cell lines in a dose-dependent manner, with IC50 values of 213 µM and 175 µM, respectively. When the viability and cytotoxicity values of the treated cells were compared, it was discovered that the cells had died of apoptosis, which was validated by DNA fragmentation analysis. Capspase 3, Bcl2 antagonist/killer, and Bcl2 associated X protein (Bax) gene expression levels all increased significantly in a quantitative investigation of apoptotic pathway genes, with 2-CT values of 2.36, 2.63, and 3.18, respectively. Conclusion: In malignant cell lines, lower quantities of the complex caused programmed cell death. This potential of complex can be used in cancer chemoprevention and cancer therapy.
1. Kanna PS, Mahendrakumar CB, Indira BN, Srivastawa S, Kalaiselvi K, Elayaraja T, et al. Chemopreventive effects of vanadium toward 1,2-dimethylhydrazine-induced genotoxicity and preneoplastic lesions in rat colon. Environ Mol Mutagen. 2004;44(2):113-8. PubMed PMID: 15278915. Epub 2004/07/28. eng.
2. Abdolmaleki A, Zahri S. Comparison of toxicity and teratogenic effects of salen and vo-salen on chicken embryo. Drug and Chemical Toxicology. 2016;39(3):344-9.
3. Samanta S, Swamy V, Suresh D, Rajkumar M, Rana B, Rana A, et al. Protective effects of vanadium against DMH-induced genotoxicity and carcinogenesis in rat colon: removal of O(6)-methylguanine DNA adducts, p53 expression, inducible nitric oxide synthase downregulation and apoptotic induction. Mutat Res. 2008 Feb 29;650(2):123-31. PubMed PMID: 18155637. Epub 2007/12/25. eng.
4. Mehdi MZ, Srivastava AK. Organo-vanadium compounds are potent activators of the protein kinase B signaling pathway and protein tyrosine phosphorylation: mechanism of insulinomimesis. Arch Biochem Biophys. 2005 Aug 15;440(2):158-64. PubMed PMID: 16055077. Epub 2005/08/02. eng.
5. Piatkowski J, Podsiadly H, Bukietynska K. The effect of V(III)-adenine complex on yeast as a model of eukaryotic cells. J Biochem. 2007 Apr;141(4):545-52. PubMed PMID: 17317691. Epub 2007/02/24. eng.
6. Kulkarni A, Patil SA, Badami PS. Synthesis, characterization, DNA cleavage and in vitro antimicrobial studies of La(III), Th(IV) and VO(IV) complexes with Schiff bases of coumarin derivatives. Eur J Med Chem. 2009 Jul;44(7):2904-12. PubMed PMID: 19155104. Epub 2009/01/22. eng.
7. Ray RS, Ghosh B, Rana A, Chatterjee M. Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: Chemopreventive activity of vanadium in vivo and in vitro. International Journal of Cancer. 2006;120:13-23.
8. Noutsopoulos D, Markopoulos G, Koliou M, Dova L, Vartholomatos G, Kolettas E, et al. Vanadium induces VL30 retrotransposition at an unusually high level: a possible carcinogenesis mechanism. J Mol Biol. 2007 Nov 16;374(1):80-90. PubMed PMID: 17920077. Epub 2007/10/09. eng.
9. Zhang Z, Huang C, Li J, Leonard SS, Lanciotti R, Butterworth L, et al. Vanadate-induced cell growth regulation and the role of reactive oxygen species. Arch Biochem Biophys. 2001 Aug 15;392(2):311-20. PubMed PMID: 11488607. Epub 2001/08/08. eng.
10. Faneca H, Figueiredo VA, Tomaz I, Goncalves G, Avecilla F, Pedroso de Lima MC, et al. Vanadium compounds as therapeutic agents: some chemical and biochemical studies. J Inorg Biochem. 2009 Apr;103(4):601-8. PubMed PMID: 19110313. Epub 2008/12/27. eng.
11. Roy S, Mondru AK, Dontamalla SK, Vaddepalli RP, Sannigrahi S, Veerareddy PR. Methoxy VO-salen stimulates pancreatic beta cell survival by upregulation of eNOS and downregulation of apoptosis in STZ-induced diabetic rats. Biological trace element research. 2011 Dec;144(1-3):1095-111. PubMed PMID: 21748304. Epub 2011/07/13. eng.
12. Mohammadi M, Yazdanparast R. Methoxy VO-salen complex: in vitro antioxidant activity, cytotoxicity evaluation and protective effect on CCl4-induced oxidative stress in rats. Food Chem Toxicol. 2009 Apr;47(4):716-21. PubMed PMID: 19152825. Epub 2009/01/21. eng.
13. Ray RS, Rana B, Swami B, Venu V, Chatterjee M. Vanadium mediated apoptosis and cell cycle arrest in MCF7 cell line. Chem Biol Interact. 2006 Nov 7;163(3):239-47. PubMed PMID: 16970931. Epub 2006/09/15. eng.
14. Boghaei DM, Bezaatpour A, Behzad M. Synthesis, characterization and catalyticactivity of novelmonomeric and polymeric vanadyl Schiffbase complexes. Journal of Molecular Catalysis A: Chemical. 2006;245(1-2):12-6.
15. Takao T, Watanabe N, Yagi I, Sakata K. A simple screening method for antioxidants and isolation of several antioxidants produced by marine bacteria from fish and shellfish. Bioscience Biotechnology and Biochemistry. 1994;58:1780-3.
16. Zahri S, Razavi SM, Moatamed Z. Antioxidant activity and cytotoxic effect of aviprin and aviprin-3''-O-D-glucopyranoside on LNCaP and HeLa cell lines. Nat Prod Res. 2011 Jun 30. PubMed PMID: 21714729. Epub 2011/07/01. Eng.
17. Zhang Q, Wu J, Hu Z, Li D. Induction of HL-60 apoptosis by ethyl acetate extract of Cordyceps sinensis fungal mycelium. Life Sci. 2004 Oct 29;75(24):2911-9. PubMed PMID: 15454342. Epub 2004/09/30. eng.
18. Zahri S, S. M. Razavi, F. H. Niri, S. Mohammadi. Induction of programmed cell death by Prangos uloptera, a medicinal plant. Biol Res. 2009;42(4):517-22. PubMed PMID: 20140307. Epub 2010/02/09. eng.
19. Zahri S, Zamani MR, Motallebi M, Sadeghi M. Cloning and characterization of cbhII gene from Trichoderma parceramosum and its expression in Pichia pastoris. Iranian Journal of Biotechnology. 2005;3(4):204-15.
20. Szymanski FM, Bakon L, Grabowski M, Piatkowski R, Filipiak KJ, Rdzanek A, et al. Previously undiagnosed congenitally corrected transposition of the great arteries in a 51-year-old woman with chronic heart failure symptoms. Int J Cardiol. 2007 Apr 4;116(3):e111-3. PubMed PMID: 17126929. Epub 2006/11/28. eng.
21. Ory K, Lebeau J, Levalois C, Bishay K, Fouchet P, Allemand I, et al. Apoptosis inhibition mediated by medroxyprogesterone acetate treatment of breast cancer cell lines. Breast Cancer Res Treat. 2001 Aug;68(3):187-98. PubMed PMID: 11727956. Epub 2001/12/01. eng.
22. Nagy B, Lundan T, Larramendy ML, Aalto Y, Zhu Y, Niini T, et al. Abnormal expression of apoptosis-related genes in haematological malignancies: overexpression of MYC is poor prognostic sign in mantle cell lymphoma. Br J Haematol. 2003 Feb;120(3):434-41. PubMed PMID: 12580957. Epub 2003/02/13. eng.
23. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001 Dec;25(4):402-8. PubMed PMID: 11846609. Epub 2002/02/16. eng.
24. Tsuchida E, Yamamoto K, Oyaizu K, Iwasaki N, Anson FC. Electrochemical Investigations of the Complexes Resulting from the Acid-Promoted Deoxygenation and Dimerization of (N,N'-Ethylenebis(salicylideneaminato))oxovanadium(IV). Inorganic chemistry. 1994;33 (6):1056–63.
25. Novotny L, Kombian SB. Vanadium: possible use in cancer chemoprevention and therapy. Journal of Cancer Research Updates. 2014;3(2):97-102.
26. Butterfield DA, Kanski J. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev. 2001 Jul 15;122(9):945-62. PubMed PMID: 11348660. Epub 2001/05/12. eng.
27. Rauscher FM, Sanders RA, Watkins JB, 3rd. Effects of isoeugenol on oxidative stress pathways in normal and streptozotocin-induced diabetic rats. J Biochem Mol Toxicol. 2001;15(3):159-64. PubMed PMID: 11424226. Epub 2001/06/26. eng.
28. Dabros W, Adamczyk A, Ciurkot K, Kordowiak AM. Vanadium compounds affect growth and morphology of human rhabdomyosarcoma cell line. Polish journal of pathology : official journal of the Polish Society of Pathologists. 2011 Dec;62(4):262-8. PubMed PMID: 22246913. Epub 2012/01/17. eng.
29. Evangelou AM. Vanadium in cancer treatment. Crit Rev Oncol Hematol. 2002 Jun;42(3):249-65. PubMed PMID: 12050018. Epub 2002/06/07. eng.
30. Sankar Ray R, Roy S, Ghosh S, Kumar M, Chatterjee M. Suppression of cell proliferation, DNA protein cross-links, and induction of apoptosis by vanadium in chemical rat mammary carcinogenesis. Biochimica et biophysica acta. 2004 Nov 18;1675(1-3):165-73. PubMed PMID: 15535980. Epub 2004/11/13. eng.
31. Abu-Qare AW, Abou-Donia MB. Biomarkers of apoptosis: release of cytochrome c, activation of caspase-3, induction of 8-hydroxy-2'-deoxyguanosine, increased 3-nitrotyrosine, and alteration of p53 gene. Journal of Toxicology and Environmental Health, Part B Critical Reviews. 2001 Jul-Sep;4(3):313-32. PubMed PMID: 11503418. Epub 2001/08/16. eng.
32. Bedner E, Li X, Kunicki J, Darzynkiewicz Z. Translocation of Bax to mitochondria during apoptosis measured by laser scanning cytometry. Cytometry. 2000 Oct 1;41(2):83-8. PubMed PMID: 11002262. Epub 2000/09/26. eng.
33. Jia L, Patwari Y, Srinivasula SM, Newland AC, Fernandes-Alnemri T, Alnemri ES, et al. Bax translocation is crucial for the sensitivity of leukaemic cells to etoposide-induced apoptosis. Oncogene. 2001 Aug 9;20(35):4817-26. PubMed PMID: 11521193. Epub 2001/08/25. eng.
34. Weng LP, Yuan J, Yu Q. Overexpression of the transmembrane tyrosine phosphatase LAR activates the caspase pathway and induces apoptosis. Current biology : CB. 1998 Feb 26;8(5):247-56. PubMed PMID: 9501065. Epub 1998/04/16. eng.
35. You M, Yu DH, Feng GS. Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway. Molecular and cellular biology. 1999 Mar;19(3):2416-24. PubMed PMID: 10022928. Pubmed Central PMCID: 84034. Epub 1999/02/18. eng.
2. Abdolmaleki A, Zahri S. Comparison of toxicity and teratogenic effects of salen and vo-salen on chicken embryo. Drug and Chemical Toxicology. 2016;39(3):344-9.
3. Samanta S, Swamy V, Suresh D, Rajkumar M, Rana B, Rana A, et al. Protective effects of vanadium against DMH-induced genotoxicity and carcinogenesis in rat colon: removal of O(6)-methylguanine DNA adducts, p53 expression, inducible nitric oxide synthase downregulation and apoptotic induction. Mutat Res. 2008 Feb 29;650(2):123-31. PubMed PMID: 18155637. Epub 2007/12/25. eng.
4. Mehdi MZ, Srivastava AK. Organo-vanadium compounds are potent activators of the protein kinase B signaling pathway and protein tyrosine phosphorylation: mechanism of insulinomimesis. Arch Biochem Biophys. 2005 Aug 15;440(2):158-64. PubMed PMID: 16055077. Epub 2005/08/02. eng.
5. Piatkowski J, Podsiadly H, Bukietynska K. The effect of V(III)-adenine complex on yeast as a model of eukaryotic cells. J Biochem. 2007 Apr;141(4):545-52. PubMed PMID: 17317691. Epub 2007/02/24. eng.
6. Kulkarni A, Patil SA, Badami PS. Synthesis, characterization, DNA cleavage and in vitro antimicrobial studies of La(III), Th(IV) and VO(IV) complexes with Schiff bases of coumarin derivatives. Eur J Med Chem. 2009 Jul;44(7):2904-12. PubMed PMID: 19155104. Epub 2009/01/22. eng.
7. Ray RS, Ghosh B, Rana A, Chatterjee M. Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: Chemopreventive activity of vanadium in vivo and in vitro. International Journal of Cancer. 2006;120:13-23.
8. Noutsopoulos D, Markopoulos G, Koliou M, Dova L, Vartholomatos G, Kolettas E, et al. Vanadium induces VL30 retrotransposition at an unusually high level: a possible carcinogenesis mechanism. J Mol Biol. 2007 Nov 16;374(1):80-90. PubMed PMID: 17920077. Epub 2007/10/09. eng.
9. Zhang Z, Huang C, Li J, Leonard SS, Lanciotti R, Butterworth L, et al. Vanadate-induced cell growth regulation and the role of reactive oxygen species. Arch Biochem Biophys. 2001 Aug 15;392(2):311-20. PubMed PMID: 11488607. Epub 2001/08/08. eng.
10. Faneca H, Figueiredo VA, Tomaz I, Goncalves G, Avecilla F, Pedroso de Lima MC, et al. Vanadium compounds as therapeutic agents: some chemical and biochemical studies. J Inorg Biochem. 2009 Apr;103(4):601-8. PubMed PMID: 19110313. Epub 2008/12/27. eng.
11. Roy S, Mondru AK, Dontamalla SK, Vaddepalli RP, Sannigrahi S, Veerareddy PR. Methoxy VO-salen stimulates pancreatic beta cell survival by upregulation of eNOS and downregulation of apoptosis in STZ-induced diabetic rats. Biological trace element research. 2011 Dec;144(1-3):1095-111. PubMed PMID: 21748304. Epub 2011/07/13. eng.
12. Mohammadi M, Yazdanparast R. Methoxy VO-salen complex: in vitro antioxidant activity, cytotoxicity evaluation and protective effect on CCl4-induced oxidative stress in rats. Food Chem Toxicol. 2009 Apr;47(4):716-21. PubMed PMID: 19152825. Epub 2009/01/21. eng.
13. Ray RS, Rana B, Swami B, Venu V, Chatterjee M. Vanadium mediated apoptosis and cell cycle arrest in MCF7 cell line. Chem Biol Interact. 2006 Nov 7;163(3):239-47. PubMed PMID: 16970931. Epub 2006/09/15. eng.
14. Boghaei DM, Bezaatpour A, Behzad M. Synthesis, characterization and catalyticactivity of novelmonomeric and polymeric vanadyl Schiffbase complexes. Journal of Molecular Catalysis A: Chemical. 2006;245(1-2):12-6.
15. Takao T, Watanabe N, Yagi I, Sakata K. A simple screening method for antioxidants and isolation of several antioxidants produced by marine bacteria from fish and shellfish. Bioscience Biotechnology and Biochemistry. 1994;58:1780-3.
16. Zahri S, Razavi SM, Moatamed Z. Antioxidant activity and cytotoxic effect of aviprin and aviprin-3''-O-D-glucopyranoside on LNCaP and HeLa cell lines. Nat Prod Res. 2011 Jun 30. PubMed PMID: 21714729. Epub 2011/07/01. Eng.
17. Zhang Q, Wu J, Hu Z, Li D. Induction of HL-60 apoptosis by ethyl acetate extract of Cordyceps sinensis fungal mycelium. Life Sci. 2004 Oct 29;75(24):2911-9. PubMed PMID: 15454342. Epub 2004/09/30. eng.
18. Zahri S, S. M. Razavi, F. H. Niri, S. Mohammadi. Induction of programmed cell death by Prangos uloptera, a medicinal plant. Biol Res. 2009;42(4):517-22. PubMed PMID: 20140307. Epub 2010/02/09. eng.
19. Zahri S, Zamani MR, Motallebi M, Sadeghi M. Cloning and characterization of cbhII gene from Trichoderma parceramosum and its expression in Pichia pastoris. Iranian Journal of Biotechnology. 2005;3(4):204-15.
20. Szymanski FM, Bakon L, Grabowski M, Piatkowski R, Filipiak KJ, Rdzanek A, et al. Previously undiagnosed congenitally corrected transposition of the great arteries in a 51-year-old woman with chronic heart failure symptoms. Int J Cardiol. 2007 Apr 4;116(3):e111-3. PubMed PMID: 17126929. Epub 2006/11/28. eng.
21. Ory K, Lebeau J, Levalois C, Bishay K, Fouchet P, Allemand I, et al. Apoptosis inhibition mediated by medroxyprogesterone acetate treatment of breast cancer cell lines. Breast Cancer Res Treat. 2001 Aug;68(3):187-98. PubMed PMID: 11727956. Epub 2001/12/01. eng.
22. Nagy B, Lundan T, Larramendy ML, Aalto Y, Zhu Y, Niini T, et al. Abnormal expression of apoptosis-related genes in haematological malignancies: overexpression of MYC is poor prognostic sign in mantle cell lymphoma. Br J Haematol. 2003 Feb;120(3):434-41. PubMed PMID: 12580957. Epub 2003/02/13. eng.
23. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001 Dec;25(4):402-8. PubMed PMID: 11846609. Epub 2002/02/16. eng.
24. Tsuchida E, Yamamoto K, Oyaizu K, Iwasaki N, Anson FC. Electrochemical Investigations of the Complexes Resulting from the Acid-Promoted Deoxygenation and Dimerization of (N,N'-Ethylenebis(salicylideneaminato))oxovanadium(IV). Inorganic chemistry. 1994;33 (6):1056–63.
25. Novotny L, Kombian SB. Vanadium: possible use in cancer chemoprevention and therapy. Journal of Cancer Research Updates. 2014;3(2):97-102.
26. Butterfield DA, Kanski J. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev. 2001 Jul 15;122(9):945-62. PubMed PMID: 11348660. Epub 2001/05/12. eng.
27. Rauscher FM, Sanders RA, Watkins JB, 3rd. Effects of isoeugenol on oxidative stress pathways in normal and streptozotocin-induced diabetic rats. J Biochem Mol Toxicol. 2001;15(3):159-64. PubMed PMID: 11424226. Epub 2001/06/26. eng.
28. Dabros W, Adamczyk A, Ciurkot K, Kordowiak AM. Vanadium compounds affect growth and morphology of human rhabdomyosarcoma cell line. Polish journal of pathology : official journal of the Polish Society of Pathologists. 2011 Dec;62(4):262-8. PubMed PMID: 22246913. Epub 2012/01/17. eng.
29. Evangelou AM. Vanadium in cancer treatment. Crit Rev Oncol Hematol. 2002 Jun;42(3):249-65. PubMed PMID: 12050018. Epub 2002/06/07. eng.
30. Sankar Ray R, Roy S, Ghosh S, Kumar M, Chatterjee M. Suppression of cell proliferation, DNA protein cross-links, and induction of apoptosis by vanadium in chemical rat mammary carcinogenesis. Biochimica et biophysica acta. 2004 Nov 18;1675(1-3):165-73. PubMed PMID: 15535980. Epub 2004/11/13. eng.
31. Abu-Qare AW, Abou-Donia MB. Biomarkers of apoptosis: release of cytochrome c, activation of caspase-3, induction of 8-hydroxy-2'-deoxyguanosine, increased 3-nitrotyrosine, and alteration of p53 gene. Journal of Toxicology and Environmental Health, Part B Critical Reviews. 2001 Jul-Sep;4(3):313-32. PubMed PMID: 11503418. Epub 2001/08/16. eng.
32. Bedner E, Li X, Kunicki J, Darzynkiewicz Z. Translocation of Bax to mitochondria during apoptosis measured by laser scanning cytometry. Cytometry. 2000 Oct 1;41(2):83-8. PubMed PMID: 11002262. Epub 2000/09/26. eng.
33. Jia L, Patwari Y, Srinivasula SM, Newland AC, Fernandes-Alnemri T, Alnemri ES, et al. Bax translocation is crucial for the sensitivity of leukaemic cells to etoposide-induced apoptosis. Oncogene. 2001 Aug 9;20(35):4817-26. PubMed PMID: 11521193. Epub 2001/08/25. eng.
34. Weng LP, Yuan J, Yu Q. Overexpression of the transmembrane tyrosine phosphatase LAR activates the caspase pathway and induces apoptosis. Current biology : CB. 1998 Feb 26;8(5):247-56. PubMed PMID: 9501065. Epub 1998/04/16. eng.
35. You M, Yu DH, Feng GS. Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway. Molecular and cellular biology. 1999 Mar;19(3):2416-24. PubMed PMID: 10022928. Pubmed Central PMCID: 84034. Epub 1999/02/18. eng.
| Files | ||
| Issue | Vol 14 No 1 (2022) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v14i1.14389 | |
| Keywords | ||
| Apoptosis, Vanadium, Salen Complex, Bax, Caspase | ||
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How to Cite
1.
Golamirad F, Zahri S, Abdolmaleki A, Bezaatpour A, Razavi SM. Vanadium oxide 3- methoxy salen, a synthetic biologically active complex against cancerous cell lines. Basic Clin Cancer Res. 2023;14(1):28-36.
