Therapeutic Potential of Quadrigemine I Against Lymphoma: Mechanistic Insights from Cell Lines and Xenograft Models Demonstrating DNA Damage, Oxidative Stress, and Pathway Regulation

Lymphoma is one of the malignant tumors that significantly threatens human health. Quadrigemine I, an indole alkaloid derived from the leaves of <i>Psychotria pilifera</i>, has been studied for its potential anti-tumor properties, but its mechanisms remain poorly understood. The CCK-8 assay was used to determine the cytotoxic effect of quadrigemine I on lymphoma cells. Flow cytometry was employed to analyze apoptosis and reactive oxygen species (ROS) levels in these cells. DNA damage was assessed by the comet assay, and the underlying mechanisms were investigated using RNA sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR). The anti-tumor activity of quadrigemine I was evaluated in tumor xenograft mice. Quadrigemine I suppressed lymphoma cell proliferation with an IC₅₀ of 0.46 µM. It induced apoptosis, promoted ROS generation, and caused DNA damage in tumor cells. RNA-seq analysis revealed that the significantly differentially expressed genes were notably enriched in the ErbB, p53, and apoptosis signaling pathways. RT-qPCR demonstrated altered expression levels of key genes in the aforementioned pathways. In vivo, quadrigemine I significantly inhibited tumor growth in xenograft mice by increasing apoptosis in tumor tissues, with reduced Ki-67 and Bcl-2 expression and elevated cleaved caspase-3 levels. Quadrigemine I may serve as a novel anti-tumor agent for lymphoma therapy.