Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
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Nanopharmaceutical Approach for Enhanced Anti-cancer Activity of Betulinic Acid in Lung-cancer Treatment via Activation of PARP: Interaction with DNA as a Target -Anti-cancer Potential of Nano-betulinic Acid in Lung Cancer-

  • Das, Jayeeta (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Samadder, Asmita (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Das, Sreemanti (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Paul, Avijit (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Khuda-Bukhsh, Anisur Rahman (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani)
  • Received : 2015.12.30
  • Accepted : 2016.02.03
  • Published : 2016.03.31
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Abstract

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

Keywords

References

  1. Pershagen G, Nordberg G, Bjorklund NE. Carcinomas of the respiratory tract in hamsters given arsenic trioxide and/or benzo[a]pyrene by the pulmonary route. Environ Res. 1984;34(2):227-41. https://doi.org/10.1016/0013-9351(84)90091-4
  2. Deng GE, Rausch SM, Jones LW, Gulati A, Kumar NB, Greenlee H, et al. Complementary therapies and integrative medicine in lung cancer: diagnosis and management of lung cancer, 3rd ed: american college of chest physicians evidence based clinical practice guidelines. Chest. 2013;DOI: 10.1378/chest.12-2364.
  3. Ellingwood F. The American Materia Medica, Therapeutics and Pharmacognosy. Portland: Eclectic Medical Publications; 1919. 470 p.
  4. Wang L, Bai L, Nagasawa T, Hasegawa T, Yang X, Sakai J, et al. Bioactive triterpene saponin from the roots of Phytolacca americana. J Nat Prod. 2008;71(1):35-40. https://doi.org/10.1021/np078012m
  5. Das J, Das S, Samadder A, Bhadra K, Khuda-Bukhsh AR. Poly (lactide-co-glycolide) encapsulated extract of phytolacca decandra demonstrates better intervention against induced lung adenocarcinoma in mice and on A549 cells. Eur J Pharm Sci. 2012;47(2):313-24. https://doi.org/10.1016/j.ejps.2012.06.018
  6. Fessi H, Puisieux F, Devissaquet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm. 1989;55(1):1-4. https://doi.org/10.1016/0378-5173(89)90270-6
  7. Samadder A, Das J, Das S, De A, Saha SK, Bhattacharyya SS, et al. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: some novel findings. Toxicol Appl Pharmacol. 2013;267(1):57-73. https://doi.org/10.1016/j.taap.2012.12.018
  8. Das S, Das J, Samadder A, Paul A, Khuda-Bukhsha AR. Strategic formulation of apigenin-loaded PLGA nanoparticles for intracellular trafficking, DNA targeting and improved therapeutic effects in skin melanoma in vitro. Toxicol Lett. 2013;223(2):124-38. https://doi.org/10.1016/j.toxlet.2013.09.012
  9. Tran PH, Prakash AS, Barnard R, Chiswell B, Ng JC. Arsenic inhibits the repair of DNA damage induced by benzo(a)pyrene. Toxicol Lett. 2002;133(1):59-67. https://doi.org/10.1016/S0378-4274(02)00088-7
  10. Samadder A, Chakraborty D, De A, Bhattacharyya SS, Bhadra K, Khuda-Bukhsh AR. Possible signaling cascades involved in attenuation of alloxan-induced oxidative stress and hyperglycemia in mice by ethanolic extzxdzract of Syzygium jambolanum: drug-DNA interaction with calf thymus DNA as target. Eur J Pharm Sci. 2011;44(3):207-17. https://doi.org/10.1016/j.ejps.2011.07.012
  11. Kong DM, Wang J, Zhu LN, Jin YW, Li XZ, Shen HX, et al. Oxidative DNA cleavage by schiff base tetraazamacrocyclic oxamido nickel(II) complexes. J Inorg Biochem. 2008;102(4):824-32. https://doi.org/10.1016/j.jinorgbio.2007.12.002
  12. Jain SS, Polak M, Hud NV. Controlling nucleic acid secondary structure by intercalation: effects of DNA strand length on coralyne-driven duplex disproportionation. Nucleic Acids Res. 2003;31(15):4608-15. https://doi.org/10.1093/nar/gkg648
  13. Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407(6805):770-6. https://doi.org/10.1038/35037710
  14. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature. 1998;391(6662):43-50. https://doi.org/10.1038/34112

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