J.C.K. Lai, W. Gao, A. Bhushan, S. Leung
Idaho State University College of Pharmacy,
Keywords: cytotoxic effects, chitosan, siver nanoparticles, gold nanoparticles, anti-cancer drugs, pancreatic cancer PANC-1 cells
Summary:Chitosan is the deacetylated product of chitin and is a linear polysaccharide. Because of its putative biocompatibility, chitosan has been employed in numerous applications, including, but not limited to, tissue engineering, wound healing, and drug delivery. Nanoparticles include all particles that possess at least one dimension less than 100 nm: they can be organic, inorganic, metallic or polymeric in nature. Nanoparticles possess a large surface-to-volume ratio which accounts for their high surface reactivity. Their favourable properties are being exploited in multiple applications, including biomedical ones. For example, nanogold and nanosilver particles have gained particular interest in biomedical applications because nanogold particles possess favourable biocompatibility and stability and nanosilver particles exhibit antimicrobial properties. Thus, these nanoparticles may have utility in applications in cancer nanotechnology. Pancreatic cancer is one of the most aggressive forms of cancer: for patients once diagnosed with it, their prognosis is abysmal and five-year survival is less than 5%. Consequently, as chemotherapeutic and radiation treatments for this disease are ineffective, there is an urgent need for new and/or improved treatment for this deadly cancer. The fusion of recent advances of material and biopharmaceutical sciences has generated novel approaches in drug discovery in seeking new and/or improved combination therapies for treating deadly cancers such as pancreatic cancer. In light of the considerations above, this study was initiated to investigate two hypotheses: (i) chitosan film can inhibit cancer cell growth; and (ii) this anti-cancer effect of chitosan is enhanced when used in combination with nanoparticles and/or existing chemotherapeutic drugs. We therefore investigated the effects of chitosan, chitosan in combination with nanoparticles (namely, nanogold or nanosilver particles), and chitosan in combinations with nanoparticles and/or three chemotherapeutic drugs (namely, Adriamycin, Methotrexate, or Cisplatin) on human pancreatic cancer PANC-1 cells. We found that chitosan, chitosan in combination with nanoparticles, and the three chemotherapeutic drugs exerted differential inhibitory effects on the survival/proliferation of PANC-1 cells. The inhibitory effects of the drugs (especially Adriamycin) on the survival/proliferation of PANC-1 cells were greater when employed in combination with chitosan and nanoparticles. Western blot analysis revealed treatment with chitosan, chitosan in combination with nanosilver particles, and chitosan in combination with Adriamycin and nanosilver particles exerted differential effects on the expression of AKT, p-AKT, ERK, and p-ERK proteins (important cell survival/proliferation signals) in PANC-1 cells. Taken together, our results provide some support for the two hypotheses stated above. Additionally, they suggest that chitosan and nanoparticles may have chemotherapeutic potential in the design of new and/or improved combination treatments in conjunction with known chemotherapeutic agents for treating pancreatic cancer.