Table 2.
Effects of SK inhibitors in breast cancer models.
| Inhibitor | Cell line/in vivo model | Observed effect | Reference |
|---|---|---|---|
| DUAL SK1/SK2 INHIBITORS (pan-SK INHIBITORS) | |||
| SKI-II | MCF-7 | Blocked breast cancer viability, clonogenic survival, and proliferation and decreased estrogen signaling in vitro | (94) |
| SKI-II | MDA-MB-468, MDA-MB-231, MDA-MB-436/ MDA-MB-468 xenograft in mice |
Inhibited triple-negative breast cancer cell growth in vitro and sensitized in vivo breast cancer xenografts to the EGFR inhibitor gefitinib | (130) |
| SKI-II | MDA-MB-231 | Increased intracellular sphingosine, decreased PKC activity and cell proliferation, increased apoptosis | (131) |
| SKI-II | MDA-MB-453 | Reduced basal and S1P/S1PR4-induced activation of ERK1/2 and modified HER2 trafficking | (126) |
| SKI-I | JC cell line (transformed murine mammary adenocarcinoma) allograft in BALB/c mice | Strong inhibition of tumor growth without overt toxicity | (132) |
| SK1-SELECTIVE INHIBITORS | |||
| SK1-I | 4T1-luc2 cell line (mouse mammary adenocarcinoma that expresses luciferase) allograft in BALB/c mice | Reduced the size and mitotic activity of the primary tumor, lymph node, and lung metastasis, and greatly decreased hem- and lymph-angiogenesis Reduced S1P levels in the tumor and in circulation | (133) |
| PF-543 | MDA-MB-231 | Impaired migration and invasion capability | (97) |
| SK1-5C | MDA-MB-231, MCF-7/ MDA-MB-231 xenograft in mice |
Dose-dependent induction of growth arrest, increase in apoptosis, and inhibition of cell proliferation Decrease in serum-secreted S1P and serum-induced phosphorylation of both ERK1/2 and AKT in MDA-MB-231 Attenuated tumor growth in a mouse MDA-MB-231 xenograft model |
(95) |
| SK-F | MDA-MB-231/ 4T1 allograft in BALB/c mice |
Reduced cell proliferation Sensitized mouse breast tumors to docetaxel | (134) |
| FTY720 | 4T1 allograft in BALB/c mice | Chemosensitization to docetaxel, allowing a 4-fold reduction in the effective dose | (123) |
EGFR, epidermal growth factor receptor; ERK, extracellular-regulated kinase; PKC, protein kinase C; HER, human epidermal growth factor; S1P, sphingosine-1-phosphate; S1PR, S1P receptor.