Parthenolide as a potential therapeutic agent for gastric cancer: Exploring oxidative stress and DNA damage

Abstract

Background: Gastric cancer (GC) is among the prevalent gastrointestinal malignancies and is the leading reason for cancer-related mortality. There is an urgent need for novel anti-cancer drugs that are highly active against GC. Parthenolide extracted from the traditional medicines houpo and xinyi is a potential small molecular agent against GC. Methods: GC cell proliferation was assessed in vitro and in vivo using Cell Counting Kit-8 (CCK-8), the colony formation assay, and a xenograft tumor model. Cell death, the cytoskeleton, and mitochondrial membrane potential were examined using TUNEL, phalloidin, and JC-1 staining, respectively. Reactive oxygen and nitrogen species (ROS and RNS, respectively) were investigated using DCFH-DA and DAF-FM DA probes. Cell metabolites were discovered using metabonomics. The degree of DNA damage in GC cells was described using the comet assay and γ-H2AX immunofluorescence staining. Subsequently, protein levels were determined using western blotting. Furthermore, DNA agarose gel electrophoresis was performed to clarify whether parthenolide bound directly to DNA. Results: The potent anti-cancer mechanisms of parthenolide were attributed to its ability to interfere with microtubule assembly, trigger an oxidative stress response, damage DNA by directly binding to DNA or generating excessive free radicals, and ultimately activate the mitochondrial pathway, leading to GC cell death. This investigation determined that parthenolide exhibited a suppressive effect on GC cells in vitro and in vivo. Conclusion: Parthenolide is a potential GC therapeutic agent.

Keywords

• Parthenolide
• Gastric cancer
• Metabonomics
• Oxidative stress
• DNA damage