The Autophagy Inhibitor Hydroxychloroquine Enhances Sensitivity of Osteosarcoma Cell Line MG-63 to Doxorubicin TreatmentHasanain K. Hasan Owadh, Bassim I. Mohammad, Sadiq J. Al-Muhana, Hamid Naji Obied, Rana A. Ghaleb, Najah R Hadi.
Autophagy is a self-energy supplier process response to stressful or fasting conditions where cell degrades and recycles intracellular constituents as an alternative way of energy source. Unfortunately Autophagy process play important role in tumor cell resistance to anticancer drugs. Osteosarcoma is the most commonly diagnosed primary malignant tumor of the bone. The present study evaluates the role of Autophagy inhibitor hydroxychloroquine (HCQ) on doxorubicin-induced cell death in Osteosarcoma cell line (MG-63). The results of current study found that doxorubicin induced Autophagy in Osteosarcoma (MG-63) cells, exhibiting an increased microtubule associated protein 1 light chain 3 (LC3)level, a decrease in SQSTM1 (p62) level, moreover using of Autophagy modulator increased in generation of reactive oxygen species (ROS) and decreased Autophagy activity and increased Osteosarcoma-cell death.
Although doxorubicin-induced cell death was enhanced by combined with HCQ but at high concentration of doxorubicin the cytotoxicity was decreased with increased Autophagy activity. These finding suggest that Autophagy attenuate cytotoxicity effect of doxorubicin by decreasing level of ROS, while HCQ improved doxorubicin-cytotoxicity on Osteosarcoma by inhibiting of Autophagy process.
Key words: Osteosarcoma, Autophagy, doxorubicin, hydroxychloroquine, MG-63.