Methyl sulfone induces loss of metastatic properties and reemergence of normal phenotypes in a metastatic cloudman S-91 (M3) murine melanoma cell line.
BACKGROUND
The most deadly form of cancer is not lung or colon, breast or prostate; it is any cancer that has become metastatic. Mortality due to metastatic melanoma, one of the most aggressive and deadly cancers, has increased steadily over the last several decades. Unfortunately, the arsenal of chemotherapeutic agents available today is most often unsuccessful at extending and improving the life expectancy of afflicted individuals. We sought to identify an effective and nontoxic agent against metastatic melanoma.


RESULTS
We chose to study Cloudman S-91 mouse melanoma cells (sub-clone M3, CCL53.1) because these cells are highly aggressive and metastatic, representing one of the deadliest types of cancer. Melanoma cells also had an experimental advantage because their morphology, which is easily monitored, relates to the physiology of metastatic cells and normal melanocytes. We chose to test methyl sulfone as a chemotherapeutic agent for two reasons. Because of its chemical structure, we speculated a potential anti-cancer activity by targeting microtubules. Equally important, methyl sulfone has a well-established safety profile in humans. Surprisingly, we found that malignant melanoma cells exposed to methyl sulfone demonstrated the loss of phenotypes characteristic of malignant cells, and the reemergence of phenotypes characteristic of healthy melanocytes. Briefly, over time methyl sulfone induced contact inhibition, loss of ability to migrate through an extracellular matrix, loss of anchorage-independent growth, proper wound healing followed by contact inhibition, irreversible senescence followed by arborization with melanosomes in arbors as seen in normal melanocytes.


CONCLUSIONS
Methyl sulfone may have clinical potential as a non-toxic agent effective against metastatic melanoma. Additionally, methyl sulfone has promise as a tool to explore molecular mechanisms of metastatic transformation as well as fundamental processes such as cell migration, contact inhibition, wound healing and cellular senescence.
Caron
Joan McIntyre
JM
Department of Cell Biology, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA. caron@nso1.uchc.edu
Bannon
Marissa
M
Rosshirt
Lindsay
L
Luis
Jessica
J
Monteagudo
Luke
L
Caron
John M
JM
Sternstein
Gerson Marc
GM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology* / Q000627:therapeutic use; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D010641:Phenotype; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
D000970:Antineoplastic Agents; D013450:Sulfones; C025910:dimethyl sulfone; D004121:Dimethyl Sulfoxide