title: Methyl Sulfone Blocked Multiple Hypoxia- and Non-Hypoxia-Induced Metastatic Targets in Breast Cancer Cells and Melanoma Cells.
abstract: Metastatic cancer causes 90% of cancer deaths. Unlike many primary tumors, metastatic tumors cannot be cured by surgery alone. Metastatic cancer requires chemotherapy. However, metastatic cells are not easily killed by chemotherapy. These problems with chemotherapy are caused in part by the metastatic cell niche: hypoxia. Here we show that the molecule, methyl sulfone, normalized metastatic metabolism of hypoxic breast cancer and melanoma cells by altering several metabolic functions of the cells. Under hypoxia, methyl sulfone decreased expression of the master regulator of hypoxia, HIF-1α, and reduced levels of the glycolytic enzymes, PKM2, LDHA, GLUT1, the pro-angiogenic protein, VEGF, and the iron-sulfur metabolism molecules, miR-210 and transferrin, all of which promote metastasis. Conversely, methyl sulfone increased levels of ISCU1/2 and ferroportin, proteins associated with iron-sulfur cluster biogenesis and iron homeostasis in normal cells. These data identify methyl sulfone as a multi-targeting molecule that blocks the survival/proliferative effect of hypoxia on metastatic cells and brings normality back to cellular metabolism.
authors.affiliation: JMCaron, LLC, Thomaston, CT, 06787, United States of America.
authors.forename: Joan McIntyre
authors.initials: JM
authors.lastname: Caron
authors.affiliation: JMCaron, LLC, Thomaston, CT, 06787, United States of America.
authors.forename: Jane McIntyre
authors.initials: JM
authors.lastname: Caron
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002675:Child, Preschool; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology*
chemical_list: C549325:MIRN210 microRNA, mouse; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D013450:Sulfones; C025910:dimethyl sulfone; D007501:Iron; D004121:Dimethyl Sulfoxide