Methyl sulfone manifests anticancer activity in a metastatic murine breast cancer cell line and in human breast cancer tissue--part I: murine 4T1 (66cl-4) cell line.

BACKGROUND: The spread of cancer (metastasis) is usually associated with death. We have identified a new approach that may be useful for treating metastatic cancer. METHODS: Here we studied the murine breast cancer cell line 66cl-4, because these cells are highly aggressive, potent inducers of metastasis and estrogen receptor negative. RESULTS: We found that 200 mM methyl sulfone did not induce apoptosis in cancerous cells but instead decreased cell proliferation and DNA synthesis, inhibited migration of cells through an extracellular matrix and induced contact inhibition and anchorage-dependent growth. Methyl sulfone promoted proper wound healing, reversed the epithelial to mesenchymal transition associated with metastatic disease and increased expression of α-smooth muscle actin, a differentiation protein of breast myoepithelial cells. CONCLUSION: Methyl sulfone did not kill the cancer cells but instead decreased metastatic phenotypes and increased normal differentiated phenotypes.

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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.