Effects of protein kinase Cdelta and phospholipase C-gamma1 on monocyte chemoattractant protein-1 expression in taxol-induced breast cancer cell death

Int J Mol Med. 2009 Dec;24(6):853-8.

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that plays an important role in immune cell migration. It has been reported that chemokines, including MCP-1, are involved in angiogenesis and metastasis. However, the exact role of chemokines in cancer development is still obscure. We investigated the involvement of MCP-1 in taxol-induced breast cancer cell death. The anti-cancer drug taxol induced MCF-7 breast cancer cell death. Treatment with taxol increased the mRNA expression level of MCP-1 in a dose- and time-dependent manner. Up-regulation of MCP-1 by taxol was augmented in cells treated with rottlerin, a specific inhibitor of protein kinase Cdelta (PKCdelta). In addition, taxol-induced MCP-1 expression was reduced by the ectopic expression of PKCdelta in a dose-dependent manner, indicating that PKCdelta plays a negative role in taxol-induced MCP-1 expression in MCF-7 cells. On the other hand, taxol-induced up-regulation of MCP-1 was reduced in cells treated with U73122, an inhibitor of phospholipase C (PLC), and ectopic expression of PLC-gamma1 increased the expression of MCP-1 in taxol-treated MCF-7 cells, indicating that PLC-gamma1 functions as a positive regulator in taxol-induced MCP-1 expression. These results indicate that MCP-1 is involved in taxol-induced breast cancer cell death and we propose that taxol induces up-regulation of MCP-1 by affecting both positive and negative regulatory signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / genetics
  • Chemokines / genetics
  • Chemokines / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Paclitaxel / pharmacology*
  • Phospholipase C gamma / metabolism*
  • Protein Kinase C-delta / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Up-Regulation / drug effects

Substances

  • Chemokine CCL2
  • Chemokines
  • RNA, Messenger
  • Protein Kinase C-delta
  • Phospholipase C gamma
  • Paclitaxel