Chukwumaobim Daniel Uzochukwuwulu Nwokwu1,
Sameera Ranganath Samarakoon1
,
Desiree Nedra Karunaratne2,
Nuwanthi P Katuvawila3,
Geethi Kaushalya Pamunuwa2,
Meran Keshawa Ediriweera1,
Kamani Hemamala Tennekoon1
1Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka;
2Department of Chemistry, Faculty of Science, University of Peradeniya;
3Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park, Mahenwatte, Pitipana, Homagama, Sri Lanka.
For correspondence:- Sameera Samarakoon
Email: sam@ibmbb.cmb.ac.lk Tel:+94772988414
Accepted: 12 August 2017
Published: 30 September 2017
Citation:
Nwokwu CD, Samarakoon SR, Karunaratne DN, Katuvawila NP, Pamunuwa GK, Ediriweera MK, et al.
Induction of apoptosis in response to improved gedunin by liposomal nano-encapsulation in human non-small-cell lung cancer (NCI-H292) cell line. Trop J Pharm Res 2017; 16(9):2079-2087
doi:
10.4314/tjpr.v16i9.6
© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Abstract
Purpose: To investigate the anti-proliferative activity of free and nanoencapsulated gedunin against human non-small-cell lung cancer (NCI-H292) cells.
Methods: Gedunin-loaded nanoliposomes (LG) were prepared using thin-film hydration method. Anti-proliferative effects of free and LD were evaluated by sulforhodamine B (SRB) assay. Apoptotic effects of gedunin-loaded liposomes were assessed by evaluating expressions of p53, Bax and survivin genes, caspase 3/7 activities, DNA fragmentation and morphological changes after staining with Hoechst 33342 and acridine orange/ethidium bromide (AO/EB).
Results: Cell proliferation data and microscopic visualization demonstrated a higher anti-proliferative activity for LG than the encapsulant (liposomes) alone. LG exhibited dose- and time-dependent 10-fold anti-proliferative activity compared to the free drug, while displaying tolerable belligerence towards normal human lung fibroblast (MRC-5) cells. Apoptosis detection assays and gene expression analysis revealed the transcriptional modulation of the apoptosis-related genes (p53, survivin and Bax), increased activity of caspase 3/7 and the condensation of nuclear chromatin, implying the induction of apoptosis by the nano-formulation in NCI-H292 cells.
Conclusion: LG may therefore be considered as a potential nano-formulation which can target non-small-cell lung cancer.
Keywords: Lung cancer, Gedunin, Liposome, Nanoencapsulation, Apoptosis, Anti-proliferative activity, Nuclear chromatin