Reactive oxygen species induced by icaritin promote DNA strand breaks and apoptosis in human cervical cancer cells

Increased production of reactive oxygen species (ROS) is a distinct feature of various types of cancer. ROS drive tumor progression and render cancer cells vulnerable to additional oxidative insult. The various natural herb compounds have been shown to induce additional production of ROS in cancer cells, although the physiological implications of ROS under these conditions are not fully determined. In the present study, icaritin, a natural compound derived from the medicinal plants Epimedium, was demonstrated to potently suppresses the proliferation of human HeLa and SiHa cervical cancer cells, without similar affects on non-cancerous CCD-1095Sk fibroblasts and 293 cells, as measured by MTT and colony formation assays. Icaritin treatment caused a rapid increase in ROS in HeLa and SiHa cells, which was followed by a prominent increase in the number of DNA strand breaks. Consequently, the levels of the pro-apoptotic protein Bax and activated caspase 3 and 9 enzymes were increased, while the levels of the anti-apoptotic proteins Bcl-2 and XIAP were downregulated. These protein expression changes were accompanied by marked induction of apoptosis in icaritin-treated cancer cells. The results suggested that the icaritin-induced ROS overload promoted cancer cell death via induction of extensive oxidative DNA damage, which subsequently resulted in large numbers of DNA strand breaks and the activation of the intrinsic apoptotic pathway.