Monensin induces cell death by autophagy and inhibits matrix metalloproteinase 7 (MMP7) in UOK146 renal cell carcinoma cell line

• Published in: In vitro cellular & developmental biology. Animal Vol. 54; no. 10; pp. 736 - 742
• Main Authors: Verma, Shiv Prakash, Das, Parimal
• Format: Journal Article
• Language: English
• Published: New York Springer Science & Business Media LLC 01.12.2018; Springer US; Society for In Vitro Biology
• Subjects: Acridine orange; Animal Genetics and Genomics; Antibiotics; Anticancer properties; antineoplastic agents; Apoptosis; Autophagy; Autophagy - drug effects; Autophagy - genetics; Biomedical and Life Sciences; Cancer therapies; Carcinoma, Renal Cell - enzymology; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cell activation; CELL AND TISSUE MODELS; Cell Biology; Cell Culture; Cell cycle; Cell death; Cell Line, Tumor; cell lines; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemotherapy; Colorectal cancer; Depolarization; Developmental Biology; Down-Regulation - drug effects; Drugs; Flow cytometry; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genes; Humans; in vitro studies; Kidney cancer; Kidney Neoplasms - enzymology; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Kinases; Life Sciences; Matrilysin; Matrix metalloproteinase; Matrix Metalloproteinase 7 - genetics; Matrix Metalloproteinase 7 - metabolism; Matrix metalloproteinases; Membrane Potential, Mitochondrial - drug effects; Metastasis; Mitochondria; mitochondrial membrane; Monensin; Monensin - pharmacology; neoplasm cells; Phagocytosis; Phase contrast; Proteins; Renal cell carcinoma; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Staining; Stem Cells; Stress response; therapeutics; toxicity testing; Transcription; Tumors; RCC; MMP7; UOK 146; Monensin; Autophagy
• ISSN: 1071-2690; 1543-706X; 1543-706X
• DOI: 10.1007/s11626-018-0298-7

Monensin is a metal ionophore used as anticancer agent in many types of cancer cells. In this study, therapeutic potential of monensin was evaluated in TFE3 translocated renal cell carcinoma (RCC) cell line UOK146. UOK146 cells were treated with different concentrations of monensin, and cell death was induced as shown by MTT assay. Autophagy was studied by LC3 western, FACS and LC3 puncta formation after monensin treatment. Mitochondrial potential was studied by staining with TMRM and FACS. Antimetastatic potential of monensin was checked by inhibition of wound closure and MMP7 expression at RNA level. Dead and floating cells after the 10 monensin treatment were observed under phase contrast microscope. FACS analysis following TMRM staining showed that mitochondrial membrane gets depolarized after monensin treatment. FACS analysis after acridine orange staining showed increased double positive (green and red) cells, and LC3 upregulation and increased LC3 punta displayed autophagy activation in UOK146 cell line after monensin treatment. These findings showed that monensin acts as antiproliferative agent, activating autophagy and downregulates PRCC-TFE3 fusion transcript in Xp11.2 translocated tumor cell line.