Molecular Mechanisms of Berberine Against Camptothecin-Resistant Strains

<p>Currently, antineoplastic agents derived from plant components are widely used to treat various malignant tumors. Especially in gynecological malignancies, camptothecins (irinotecan, topotecan) are often selected for tumors refractory to first-line drugs or for recurrent tumors. Camptothecin exerts its antineoplastic effect by inhibiting DNA topoisomerase I, an enzyme that removes the DNA super helix, causing cell death. However, some malignancies are resistant to camptothecin. Herein, we focused on berberine, a component of the herbal drug Coptis Rhizome, as a potential antineoplastic agent for camptothecin-resistant malignant tumors. In our previous study, we identified several crude drug components that induce DNA double-strand breaks using pulsed-field electrophoresis in crude drug-derived extracts (120 species in total, provided by the University of Toyama) (Kawashima et al. Genes to Cells, 2017). Berberine has been reported to inhibit DNA topoisomerase II. In this study, we aimed to elucidate the molecular mechanism of the antitumor effect of berberine on camptothecin-resistant tumor cells. Two strains of acute lymphoblastic leukemia cells with camptothecin-resistant mutations, CEM/C2 (parental strain CCRF-CEM) and CPT-K5 (parental strain RPMI 8402), were used. MTT assays were performed to evaluate cell death induced by berberine, coptisine, and berberrubine, suggesting that in berberine, cell death in camptothecin-resistant strains is induced via DNA double-strand break activity. Berberine may be effective against camptothecin-resistant malignant tumors.</p>