Semaphorin 3A suppresses tumor growth and metastasis in mice melanoma model

PLoS One. 2012;7(3):e33633. doi: 10.1371/journal.pone.0033633. Epub 2012 Mar 20.


Background: Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A) acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation.

Methodology/principal findings: In this study, using multiple in vitro and in vivo approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor in vitro and in vivo mice (C57BL/6) models. Mouse melanoma (B16F10) cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of in vivo tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents.

Conclusions: Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents, Alkylating / pharmacology
  • Apoptosis / drug effects
  • Blotting, Western
  • Case-Control Studies
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Curcumin / pharmacology
  • Dacarbazine / pharmacology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Immunoenzyme Techniques
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / secondary*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary*
  • Male
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology*
  • Melanoma, Experimental / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / prevention & control
  • Phosphorylation / drug effects
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Semaphorin-3A / genetics
  • Semaphorin-3A / metabolism*
  • Wound Healing / drug effects


  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • RNA, Messenger
  • Semaphorin-3A
  • Dacarbazine
  • Curcumin