Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing Reactive Oxygen Species Production in Bladder Cancer In Vitro

Abstract

Bladder cancer remains one of the most common malignant tumors that threatens human health worldwide. It imposes a heavy burden on patients and society due to the high medical costs associated with its easy metastasis and recurrence. Although several treatment options for bladder cancer are available, their clinical efficacy remains unsatisfactory. Therefore, actively exploring new drugs and their mechanisms of action for the clinical treatment of bladder cancer is very important. Scabertopin is one of the major sesquiterpene lactones found in Elephantopus scaber L. Sesquiterpene lactones are thought to have fairly strong anti-cancer efficacy. However, the anticancer effect of sesquiterpenoid scabertopin on bladder cancer and its mechanism are still unclear. The aim of this study is to evaluate the antitumor activity of scabertopin in bladder cancer and its potential molecular mechanism in vitro. Our results suggest that scabertopin can induce RIP1/RIP3-dependent necroptosis in bladder cancer cells by promoting the production of mitochondrial reactive oxygen species (ROS), inhibit the expression of MMP-9 by inhibiting the FAK/PI3K/Akt signaling pathway, and ultimately inhibit the migration and invasion ability of bladder cancer cells. At the same time, we also demonstrated that the half-inhibition concentration (IC50) of scabertopin on various bladder cancer cell lines (J82, T24, RT4 and 5637) is much lower than that on human ureteral epithelial immortalized cells (SV-HUC-1). The above observations indicate that scabertopin is a potential therapeutic agent for bladder cancer that acts by inducing necroptosis and inhibiting metastasis.

An anti-liver tumor ingredient of Elephantopus tomentosus Linn. and the mechanism prediction by combining UPLC-Q-TOF-MS/MS, network pharmacology analysis and validating on HepG2

“…We previous suggested that ST showed a signi cantly inhibition on A549 11 , and the anti-cancer effect of ST was also validated on bladder cancer cell 32 . In this study, we rstly validated the anti-cancer effect of ST on HepG2 and elucidated the potential mechanism.…”

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis

“…Scabertopin is one of the major sesquiterpene lactones derived from Elephantopus scaber L. We found only one study on the apoptosis-inducing effects of scabertopin on cancer cells. Gao et al (2022) conducted a study to explore the anticancer effects of scabertopin on three bladder cancer cell lines (J82, T24, RT4, and 5637). The results showed that scabertopin treatment significantly suppressed the proliferation of all three bladder cancer cell lines.…”

Targeting Cell Signaling Pathways in Lung Cancer by Bioactive Phytocompounds

“…Scabertopin Scabertopin (Figure 7), a germacrane-type sesquiterpene is derived from Elephantopus scaber. It has displayed an anticancer effect in bladder cancer by modulating ROS and intracellular signaling [382]. In a xenograft mouse model of lung cancer, scabertopin was shown to promote cancer cell death through increased Bax expression and ROS-mediated apoptosis at a dose of 20 mg/kg [310].…”