Curcumin and Afatinib Synergistically Inhibit Growth of Human Osteosarcoma Cells by Inhibition of Matrix Metallo Proteinases, Mitogen Activated kinases 1-4, and Reactive Oxygen Species

Abstract

Osteosarcoma (OS) is the most common form of bone cancer in humans, primary affecting children and adolescence. OS can metastasis to lung and other bones. The five years’ survival rate of OS are only about 55-70% and if metastases is less than 20%. Chemotherapeutic drugs have been used but these drugs also caused high toxicity to normal cells; therefore, alternative chemotherapy are needed to possibly use lower amount of these drugs. Natural products with anti-cancer properties may provide synergistic effect along with chemotherapeutic drugs. Present study was aimed to evaluate our hypothesis that the combination of curcumin (CUR), a natural antioxidant, and a lower dose of afatinib (AF), an anti-cancer second generation tyrosine kinase inhibitor (TKI), would have a synergistic effect on human Saos-2 cells based on results from MTT assay, Hoechst 33342, Nuclear ID Red/Green and Rhodamine 123 staining, and Western Blot. Based on different signaling pathway being affected, CUR at 30 ?M enhanced the chemotherapeutic activity of low dose AF at 3 µM in causing cell death as compared to AF alone at high dose. Results from this study showed possible use of low dose AF with CUR to be a treatment option for osteosarcoma.