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Induction of apoptosis in response to improved gedunin by liposomal nano-encapsulation in human non-small-cell lung cancer (NCI-H292) cell line
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. Antiproliferative 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 nonsmall-cell lung cancer.
Keywords: Lung cancer, Gedunin, Liposome, Nanoencapsulation, Apoptosis, Anti-proliferative activity, Nuclear chromatin