Enhancing the anticancer effects of rosmarinic acid in PC3 and LNCaP prostate cancer cells using titanium oxide and selenium-doped graphene oxide nanoparticles
Maryam Ranjbar, Elham Einafshar, Hossein Javid, Niloufar Jafari, Seyedeh Sara Sajjadi, R. Azarian, Seyed Isaac Hashemy
Abstract
Prostate cancer remains a significant health concern due to its high mortality rate, emphasizing the need for innovative therapeutic approaches. This study aims to explore the potential anticancer effects of a drug nanocomplex containing rosmarinic acid in the treatment of prostate cancer, aiming to contribute to the development of safer and more effective treatment options for cancer patients. Nanocomposite Graphene Oxide was synthesized following the Hummers’ method. The resulted product dissolved in deionized water with rosmarinic acid to prepare the final product. To investigate the effects of rosmarinic acid@Se-TiO 2 -GO, PC3, LNCaP, and normal (HFF-1) cell lines were treated with varying concentrations (7.8, 15.6, 31.2, 62.5, 125, 250, and 500 µg/ml) of the nanocomplex. Cell viability was assessed using the Resazurin test, while levels of reactive oxygen species (ROS), gene expression ( Bcl-2 and Bax ), and total antioxidant capacity were measured in both cancerous and normal cells. The Se-TiO 2 -GO nanoparticles demonstrated high entrapment efficiency and loading capacity for rosmarinic acid. The IC50 values after 24 and 48 h of RA treatment were significantly greater than those recorded for treatments involving rosmarinic acid@Se-TiO 2 -GO. Treatment with rosmarinic acid@Se-TiO 2 -GO resulted in decreased cell viability and increased apoptosis in PC3 and LNCaP cells, while showing no inhibitory effects on the normal cell line (HFF-1) at concentrations toxic to cancer cells. Additionally, a dose-dependent increase in ROS levels, a decrease in total antioxidant capacity, elevated Bax gene expression, and reduced Bcl-2 expression were observed in the cancer cells following treatment with the nanocomplex. The cytotoxic effects of rosmarinic acid@Se-TiO 2 -GO nanoparticles on prostate cancer cells appear to be mediated through the generation of oxidative stress and induction of apoptosis. The unique formulation of these nanoparticles holds promise for future prostate cancer treatment strategies.