Acute generation of reactive oxygen species that induced by doxycycline pretreatment results in rapid cell death in polyphyllin G‐treated osteosarcoma cell lines

Abstract

Polyphyllin G, a pennogenyl saponin extracted from Paris polyphylla, has been shown to possess antitumor effects. In this study, we demonstrated that doxycycline, an antibiotic medicine, could significantly enhance the sensitivities of osteosarcoma cell lines to polyphyllin G. As the cells were pretreated with doxycycline at non-toxic concentrations and then co-exposed to polyphyllin G, this combination could induce a rapid cell death distinct from apoptosis. The non-apoptotic cell death was characterized by a loss of integrity of plasma membrane without externalization of phosphatidyl serine. Furthermore, this combined treatment resulted in suppression of cell viability and colony-forming ability, and increased the level of γ-H2A.X, a critical marker for DNA damage, in osteosarcoma cell lines. When examining the underlying mechanism, it was revealed combination of polyphyllin G and doxycycline triggered an enhanced generation of reactive oxygen species (ROS), and up-regulated mitochondrial oxidative stress within 0.5 h. Co-administration of the ROS inhibitor NAC reversed the suppressed cell viability and colony-forming ability, and abolished the increased level of γ-H2A.X in the cells with the combined treatment, indicating that the enhanced ROS was involved in the anti-proliferative effect of the combined treatment. Overall, the results demonstrated that doxycycline may function as chemosensitizers by inducing an acute and lethal ROS production to enhance cytotoxic of Shih-Chieh Hung and Yi-Fu Huang contributed equally to this study.

Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

“…Osteosarcoma is a highly prevalent bone tumor in people of all ages [ 29 ]. The traditional clinical treatment schemes mainly include preoperative chemotherapy, surgical limb salvage, and postoperative adjuvant chemotherapy [ 30 ]. However, in the last 20 years, the average survival rate of patients has remained stable at 65%–70% with no significant improvement [ 31 ].…”

NEDD4L inhibits migration, invasion, cisplatin resistance and promotes apoptosis of bladder cancer cells by inactivating the p62/Keap1/Nrf2 pathway

“…31,32 Drug resistance is a major cause of increased risk of relapse and death in cancer patients. 34,35 DDP is a commonly used chemotherapeutic agent with therapeutic effects on a wide range of cancers. [36][37][38][39][40][41][42][43][44] DDP has been considered to be a major agent in the treatment of BLCA, especially the muscle invasive BLCA.…”

“…Drug resistance is a major cause of increased risk of relapse and death in cancer patients 34,35 . DDP is a commonly used chemotherapeutic agent with therapeutic effects on a wide range of cancers 36–44 .…”