RESUMEN
Reactive oxygen species (ROS) induces necroptotic and ferroptosis in melanoma cells. Salidroside (SAL) regulates ROS in normal cells and inhibits melanoma cell proliferation. This study used human malignant melanoma cells treated with SAL either alone or in combination with ROS scavenger (NAC) or ferroptosis inducer (Erastin). Through cell viability, wound healing assays, and a Seahorse analyze found that SAL inhibited cell proliferation, migration, extracellular acidification rate, and oxygen consumption rate. Metabolic flux analysis, complexes I, II, III, and IV activity of the mitochondrial respiratory chain assays, mitochondrial membrane potential assay, mitochondrial ROS, and transmission electron microscope revealed that SAL induced mitochondrial dysfunction and ultrastructural damage. Assessment of malondialdehyde, lipid ROS, iron content measurement, and Western blot analysis showed that SAL activated lipid peroxidation and promoted ferroptosis in A-375 cells. These effects were abolished after NAC treatment. Additionally, SAL and Erastin both inhibited cell proliferation and promoted cell death; SAL increased the Erastin sensitivity of cells while NAC antagonized it. In xenograft mice, SAL inhibited melanoma growth and promoted ROS-dependent ferroptosis. SAL induced mitochondrial dysfunction and ferroptosis to block melanoma progression through ROS production, which offers a scientific foundation for conducting SAL pharmacological research in the management of melanoma.
Asunto(s)
Proliferación Celular , Ferroptosis , Glucósidos , Melanoma , Mitocondrias , Fenoles , Especies Reactivas de Oxígeno , Ferroptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Humanos , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Melanoma/patología , Fenoles/farmacología , Glucósidos/farmacología , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proliferación Celular/efectos de los fármacos , Ratones , Línea Celular Tumoral , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacosRESUMEN
Spirostomum is a genus of large ciliates, and its species are distributed worldwide. However, there has been limited research conducted on their geographical distribution and genomics. We obtained nine samples of ciliates from eight regions in Liaoning Province, China, and conducted a study on their geographical distribution and characteristics. Morphological and second-generation high-throughput sequencing methods were applied to identify the species, and a phylogenetic tree was established to gain a deeper understanding of the geographical distribution and evolutionary relationships of Spirostomum in Northeast China. The results identified Spirostomum yagiui and Spirostomum subtilis as a newly recorded species in Northeast China region. There are now five species of Spirostomum that have been recorded in China, and new details on the genomic characteristics of Spirostomum yagiui were provided. In addition, this study also identified the main branches of Spirostomum teres and Spirostomum minus in northern China, and provided a theoretical basis for the existence of hidden species. Spirostomum yagiui is the first species in the family Spirostomidae to have undergone mitochondrial genome sequencing.