Regulation of metastatic potential by drug repurposing and mitochondrial targeting in colorectal cancer cells

作者：Shashank Mathur, Pransu Srivastava, Anubhav Srivastava, Neeraj Kumar, Sabiya Abbas, Ashok Kumar, Meenakshi M. Tiwari, Lokendra Kumar Sharma · 发表于：BMC Cancer · 年份：2024 · DOI：10.1186/s12885-024-12064-5 · 被引用次数：17 · 研究领域：Mitochondrial Function and Pathology、Cancer Research and Treatments、Cancer, Hypoxia, and Metabolism

BACKGROUND: Increased mitochondrial activities contributing to cancer cell proliferation, invasion, and metastasis have been reported in different cancers; however, studies on the therapeutic targeting of mitochondria in regulating cell proliferation and invasiveness are limited. Because mitochondria are believed to have evolved through bacterial invasion in mammalian cells, antibiotics could provide an alternative approach to target mitochondria, especially in cancers with increased mitochondrial activities. In this study, we investigated the therapeutic potential of bacteriostatic antibiotics in regulating the growth potential of colorectal cancer (CRC) cells, which differ in their metastatic potential and mitochondrial functions. METHODS: A combination of viability, cell migration, and spheroid formation assays was used to measure the effect on metastatic potential. The effect on mitochondrial mechanisms was investigated by measuring mitochondrial DNA copy number by qPCR, biogenesis (by qPCR and immunoblotting), and functions by measuring reactive oxygen species, membrane potential, and ATP using standard methods. In addition, the effect on assembly and activities of respiratory chain (RC) complexes was determined using blue native gel electrophoresis and in-gel assays, respectively). Changes in metastatic and cell death signaling were measured by immunoblotting with specific marker proteins and compared between CRC cells. RESULTS: Both tigecycline and tetracycline effecti...