Cyperotundone combined with adriamycin induces apoptosis in MCF-7 and MCF-7/ADR cancer cells by ROS generation and NRF2/ARE signaling pathway

Breast cancer has become the most prevalent cancer, globally. Adriamycin is a first-line chemotherapeutic agent, however, cancer cells acquire resistance to it, which is one of the most common causes of treatment failure. ROS and NRF2 are essential oxidative stress factors that play a key role in the oxidative stress process and are associated with cancer. Our goal is to create novel therapeutic drugs or chemical sensitizers that will improve chemotherapy sensitivity. The optimal concentration and duration for MCF-7 and MCF-7/ADR cells in ADR and CYT were determined using the CCK-8 assay. We found that ADR + CYT inhibited the activity of MCF-7 and MCF-7/ADR cells in breast cancer, as well as causing apoptosis in MCF-7 and MCF-7/ADR cells and blocking the cell cycle in the G0/G1 phase. ADR + CYT induces apoptosis in MCF-7 and MCF-7/ADR cells through ROS generation and the P62/NRF2/HO-1 signaling pathway. In breast cancer-bearing nude mice, ADR + CYT effectively suppressed tumor development in vivo. Overall, our findings showed that CYT in combination with ADR has potent anti-breast cancer cell activity both in vivo and in vitro, suggesting CYT as the main drug used to improve chemosensitivity.

Automated summary

Breast cancer is the most prevalent cancer worldwide, and resistance to the first-line chemotherapeutic agent Adriamycin is a common cause of treatment failure. The study focuses on the role of oxidative stress factors ROS and NRF2 in breast cancer and aims to develop therapeutic drugs that can enhance chemotherapy sensitivity. The combination of ADR and CYT showed potent anti-breast cancer activity by inhibiting cell activity, inducing apoptosis, and blocking the cell cycle in breast cancer cells through ROS generation and the P62/NRF2/HO-1 signaling pathway. The effectiveness of ADR + CYT in suppressing tumor development was also observed in breast cancer-bearing mice.