(256i) Evaluation of the Cancer-Preventive Effect of Resveratrol-Loaded Nanoparticles on the Formation of Tumor Spheroids

Evaluation of the cancer-preventive effect of resveratrol-loaded nanoparticles on the formation of tumor spheroids

Elisa A. Torrico-Guzman¹, Mitchell Gravely¹, Samantha A. Meenach^1,2

¹Department of Chemical Engineering, ²Department of Biomedical & Pharmaceutical Sciences, University of Rhode Island, Kingston, RI

Cancer is the second leading cause of mortality in the U.S. following heart disease. In 2015 it is expected that 1,658,350 new cases of cancer will be diagnosed in the U.S.. Nearly one-third of cancer-related deaths in the U.S. each year are caused by tobacco smoking. Moreover, one-third of the cancer cases in the U.S. are related to obesity, physical inactivity, and/ or poor nutrition, which can be prevented [1]. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or inhibit the carcinogenic process resulting in a decreased cancer risk [2] and has been successfully applied to common malignancies. The FDA has approved some drugs as cancer prevention agents such as: Tamoxifen for breast cancer and the Human Papiloma Virus (HPV) vaccine for cervical intraepithelial neoplasia and cancer. More than 200 other drugs are in clinical trial not yet with reported results [3].

Resveratrol (RSV) is a natural phenol with antioxidant, anti-inflammatory properties, and beneficial effects against cancer. It can be found in many plants including red grapes, peanut butter, dark chocolate and blueberries.  A study by Dolfini [4] showed that RSV induces drastic growth inhibition on a human breast cancer cell line in vivo and in vitroassays. Furthermore, RSV-loaded gel nanoparticles enhanced intracellular uptake and cytotoxicity in a NCI-H460 lung cancer cell line [5]. Moreover, RSV loaded into nanostructures lipid carriers (NLC) exhibit higher penetration into the skin in comparison to solid lipid nanoparticles (SLN) [6], which demonstrates the improvement of RSV in nanoparticle (NP) systems.

In this project we have evaluated the ability of resveratrol-loaded nanoparticles to prevent the growth of tumor spheroids. RSV was loaded into nanoparticles based on a biodegradable polymer acetalated dextran (Ac-Dex). Then, free RSV and RSV NP were tested in two-dimension (2D) and three-dimension (3D) cell culture in order to evaluate the viability of the A549 lung cancer cell line. So far, RSV exerted an inhibitory effect over the growth of cancer cells, showing a promising alternative as a chemopreventive drug, which could palliate the incidence or mortality from cancer.

REFERENCES

1.         Siegel, R.L., K.D. Miller, and A. Jemal, Cancer statistics, 2015. CA Cancer J Clin, 2015. 65(1): p. 5-29.

2.         Sporn, M.B., et al., Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc, 1976. 35(6): p. 1332-8.

3.         Davis, J.S. and X. Wu, Current state and future challenges of chemoprevention. Discov Med, 2012. 13(72): p. 385-90.

4.         Dolfini, E., et al., Resveratrol impairs the formation of MDA-MB-231 multicellular tumor spheroids concomitant with ceramide accumulation. Cancer Lett, 2007. 249(2): p. 143-7.

5.         Karthikeyan, S., et al., Anticancer activity of resveratrol-loaded gelatin nanoparticles on NCI-H460 non-small cell lung cancer cells. Biomedicine & Preventive Nutrition, 2013. 3(1): p. 64-73.

6.         Gokce, E.H., et al., Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications. Int J Nanomedicine, 2012. 7: p. 1841-50.