Ustusolate E and 11α-Hydroxy-Ustusolate E induce apoptosis in cancer cell lines by regulating the PI3K/AKT/mTOR and p-53 pathways

Cancer is a major disease that affects human health and longevity. The global cancer burden is projected to increase by 47% by 2040 compared to 2020, and the global economic burden of cancer will further increase. Therefore, new alternate drugs are urgently needed to reduce the global burden of cancer. Natural products play a very important role in the discovery and development of anticancer drugs. Here, we isolated Ustusolate E (UE) and its analog 11α-Hydroxy-Ustusolate E (HUE) from strain A. calidoustus TJ403-EL05, detected the antitumor activities of both, and explored their mechanisms of action. We found that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells) induced irreversible DNA damage, blocked the cell cycle at the G2/M phase, and further induced apoptosis in tumor cells. To our knowledge, this is the first report on the anticancer effects of UE and HUE and their mechanisms. The present study suggests that compounds HUE and UE could be used as lead compounds for anticancer drug development.