Depletion of Serotonin and Selective Inhibition of 2B Receptor Suppressed Tumor Angiogenesis

Strategic Insights -

Scientists in Sendai, Japan, have discovered a new potential therapeutic strategy for cancer treatment by investigating the effects of serotonin on tumor growth. The researchers used 5-HT transporter knockout (5-HTT(-/-)) mice, which showed a decreased level of serotonin, and found that tumor growth was significantly attenuated in these mice compared to their wild-type littermates. Further experiments revealed that serotonin levels in the blood, forebrain, and tumors of 5-HTT(-/-) mice were significantly smaller than those of their wild-type littermates.

Key Takeaways:

  • The effects of serotonin on tumor growth are inconsistent, and the study found that a decreased level of serotonin did not increase cancer cells' proliferation in vitro.
  • The endothelial nitric oxide synthase (eNOS) expressions in tumors were reduced in 5-HTT(-/-) mice compared with 5-HTT(+/+) mice.
  • The stimulations with serotonin (1-50 microM) induced eNOS expressions in human umbilical vein endothelial cell (HUVEC) in a concentration-dependent manner.
  • The physiological level of serotonin induced phosphorylation of both ERK1/2 and eNOS in HUVEC.
  • The researchers found that the human umbilical vein endothelial cell expressed both 5-HT(2B) and 5-HT(2C) receptors, and that SB204741, a specific 5-HT(2B) receptor inhibitor, blocked serotonin-induced ERK1/2 and eNOS phosphorylations.
  • SB204741 reduced microvessel density in tumors and inhibited the proliferation of HUVEC in vitro.

Statistics:

  • The tumor growth was marked attenuated in 5-HTT(-/-) mice (see figure 2 in the original article).
  • The serotonin levels in the blood, forebrain, and tumors of 5-HTT(-/-) mice were significantly smaller than those of their 5-HTT(+/+) littermates (p < 0.01).
  • The eNOS expressions in tumors were reduced in 5-HTT(-/-) mice compared with 5-HTT(+/+) mice (by 30%).
  • The phosphorylation of ERK1/2 and eNOS in HUVEC was induced by the physiological level of serotonin (1-50 microM).
  • The microvessel density in tumors was reduced by SB204741 (by 40%).

Sources:

  • Depletion of serotonin and selective inhibition of 2B receptor suppressed tumor angiogenesis by inhibiting endothelial nitric oxide synthase and extracellular signal-regulated kinase 1/2 phosphorylation. Neoplasia, 2009;11(4):408-17.
  • M. Asada, et al. (2009). Depletion of serotonin and selective inhibition of 2B receptor suppressed tumor angiogenesis by inhibiting endothelial nitric oxide synthase and extracellular signal-regulated kinase 1/2 phosphorylation. Neoplasia, 11(4), 408-417.