Study of the enhanced anticancer efficacy of gambogic acid on Capan-1 pancreatic cancer cells when mediated via magnetic Fe3O4 nanoparticles

Abstract

Background: Gambogic acid (GA), a potent anticancer agent, is limited in clinical administration due to its poor water solubility. The aim of this study was to explore a drug delivery system based on magnetic Fe(3)O(4) nanoparticles (MNP-Fe(3)O(4)) conjugated with GA to increase water solubility of the drug and enhance its chemotherapeutic efficiency for pancreatic cancer.

Methods: GA was conjugated with the MNP-Fe(3)O(4) colloidal suspension by mechanical absorption polymerization to construct GA-loaded MNP-Fe(3)O(4), which acted as a drug delivery system.

Results: Combination therapy with GA and MNP-Fe(3)O(4) induced remarkable improvement in anticancer activity, which was demonstrated by optical microscopic observations, MTT assay, and nuclear DAPI staining. Furthermore, the possible signaling pathway was explored by Western blot. In Capan-1 pancreatic cancer cells, our observations demonstrated that this strategy could enhance potential anticancer efficiency by inducing apoptosis. The mechanisms of the synergistic effect may be due to reducing protein expression of Bcl-2 and enhancing that of Bax, caspase 9, and caspase 3.

Conclusion: These findings demonstrate that a combination of GA and MNPs-Fe(3)O(4) represents a promising approach to the treatment of pancreatic cancer.

Keywords: apoptosis; drug delivery system; gambogic acid; magnetic nanoparticles; pancreatic cancer.

Figure 1

Transmission electron microscope image of magnetic Fe₃O₄ nanoparticles.

Figure 2

Size distribution histogram of magnetic Fe₃O₄ nanoparticles.

Figure 3

Cytotoxic effect of GA or GA-loaded MNP-Fe₃O₄ against the Capan-1 pancreatic cancer cells. Inset: Microscopic images of the Capan-1 cells after different treatments for 48 hours. (A) untreated cells as control, (B) MNP-Fe₃O₄, (C) GA alone, and (D) GA-loaded MNP-Fe₃O₄. Notes: The concentrations of GA, MNP-Fe₃O₄ are 1 μmol/L and 20 μg/mL, respectively. Data are expressed as means ± standard deviations (n − 3). Abbreviations: GA, gambogic acid; MNP-Fe₃O₄, magnetic Fe₃O₄ nanoparticles.

Figure 4

Nuclear morphologic changes of the Capan-1 pancreatic cancer cells after different treatment for 48 hours. (A) untreated cells as control, (B) MNP-Fe₃O₄, (C) GA alone, and (D) GA-loaded MNP-Fe₃O₄. Notes: The concentrations of GA and MNP-Fe₃O₄ are 1 μmol/L and 20 μg/mL, respectively. Magnification folds ×400. Arrows indicate cells with apoptotic nuclear condensation and fragmentation. Abbreviations: GA, gambogic acid; MNP-Fe₃O₄, magnetic Fe₃O₄ nanoparticles.

Figure 5

Expression of Bax, Bcl-2, caspase 3, and caspase 9 protein in the Capan-1 pancreatic cancer cells by Western blot after treatment of GA and/or MNP-Fe₃O₄ for 48 hours. Line 1, control; Line 2, incubated with 20 mg/L MNP-Fe₃O₄; Line 3, incubated with 1 μmol/L GA; Line 4, incubated with 1 μmol/L GA and 20 μg/mL MNP-Fe₃O₄. Abbreviations: MNP-Fe₃O₄, magnetic nanoparticles of Fe₃O₄; GA, gambogic acid.

Figure 6

Schematic illustration of the possible process of distinguished improvement in anticancer activity by the GA-loaded MNP-Fe₃O₄. Abbreviations: MNP-Fe₃O₄, magnetic nanoparticles of Fe₃O₄; GA, gambogic acid.