Effects of Retinoic Acid-induced PKC-d on the Insulin Like Growth Factor-I (IGF-I)System is Involved in Reactive Oxygen Species (ROS) in MCF-7 Cells

All-trans retinoic acid (RA) as a useful therapeutic anti-cancer agent is known to induce apoptosis and growth inhibition of human breast cancer cells (MCF- 7 cells). Whereas insulin like growth factor-I (IGF-I) plays an important role in proliferation of cancer cells. RA dose- and time- dependency decreased in the level of secretion and synthesis of IGF-I. The treatment with 10' M RA for 72h significantly increased in the phospho-protein kinase C (PKC)-delta activity. PKC-delta inhibitor rottlerin prevented the Ra-induced inhibition of secretion and synthesis of IGF-I. The treatment with 10' M RA for 72h also increased the level of TEARS, and the increase was blocked by rottlerin as well as antioxidants such as GSH and DPI. Similarly these antioxidants also recovered the RA-induced inhibition of secretion and synthesis of IGF-I. These results indicate that RA-induced inhibition of secretion and synthesis of IGF-I were associated with the PKC-delta dependent mechanism and put in evidence that the interaction of PKC-delta and ROS.