Background: Cell migration is an essential process for survival and differentiation of mammalian cells.
Numerous diseases are induced or influenced by inappropriate regulation of cell migration, which plays a key role in
cancer cell metastasis. In fact, very few anti-metastasis drugs are available on the market. SphKs are enzymes that
convert sphingosine to sphingosine-1-phosphate (S1P) and are known to control various cellular functions, including
migration of cells. In human, SphK2 is known to promote apoptosis, suppresses cell growth, and controls cell
migration; in addition, the specific ablation of SphK2 activity was reported to inhibit cancer cell metastasis.
Objective: The previously identified SG12 and SG14 are synthetic analogs of sphingoid and can specifically
inhibit the functions of SphK2. We investigated the effects of the SphK2 specific inhibitors on the migratory
behavior of cells.
Method: We investigated how SG12 and SG14 affect cell migration by monitoring both cumulative and individual
cell migration behavior using HeLa cells.
Results: SG12 and SG14 mutually showed stronger inhibitory effects with less cytotoxicity compared with a
general SphK inhibitor, N,N-dimethylsphingosine (DMS). The mechanistic aspects of specific SphK2 inhibition
were studied by examining actin filamentation and the expression levels of motility-related genes.
Conclusion: The data revealed that SG12 and SG14 resemble DMS in decreasing overall cell motility, but differ
in that they differentially affect motility parameters and motility-related signal transduction pathways and
therefore actin polymerization, which are not altered by DMS. Our findings show that SphK2 inhibitors are
putative candidates for anti-metastatic drugs.