Synthetic antioxidants from a natural source can overtake the oncogenic stress management system and activate thestress‑sensitized death of KSHV‑infected cancer cells.

Abstract

Synthetic and modified natural derivatives are reported as potential bioactive compounds and are being used therapeutically against various diseases in a wide-spread manner nowadays. Cancerous cells exhibit high levels of reactive oxygen species (ROS) internally, and thus successfully manage to sustain themselves and proliferate via antioxidative mechanisms that maintain a redox balance. On this note, various antioxidants are applied as anticancer compounds, which strategically affects the ongoing oncogenic stress management system in both a pro- and antioxidative manner, resulting in cancer restriction, as well as sustaining cell proliferation via antioxidative mechanisms that promote cancer progression. Alike non-viral cancers, viral cancers exhibit varying levels of ROS during different stages of cancer progression. Hence, successful stress balance should be addressed, depending on the cancer cell stress response during the therapeutic management. The application of antioxidants is crucial and needs to be carefully designed in such cases; the respective underlying mechanisms are less understood. The role of antioxidants controlling the varied levels of stress response at different stages of Kaposi's sarcoma-associated herpes virus malignancy have not been fully reported. Therefore, the present study aimed to analyze the activity of certain antioxidants in KSHV-infected oncogenic cells. For this purpose, two naturally derived flavonoid-based antioxidants (theaflavin and novel curcumin derivatives) were selected and tested in different KSHV-infected cell lines. The findings presented herein demonstrate that these compounds can successfully induce the death of different KSHV-positive cells and can restrict the growth of KSHV-infected cell lines restricting viral reactivation by counteracting the oncogenic stress management system.