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Cyclic phosphatidic acid induces G0/G1 arrest, inhibits Akt phosphorylation, and downregulates cyclin D1 expression in colorectal cancer cells

Abstract

Lysophosphatidic acid (LPA) and its analogs are well-known mitogens for various cell types. Many reports have confirmed that several types of cancer cell produce LPA to promote survival, growth and tumorigenesis. This indicates that the interface between the LPA signaling pathway and the cell cycle signaling system is critical to the control of cancer cell proliferation. However, our previous study indicated that cyclic phosphatidic acid (cPA), which is structurally similar to LPA, inhibits the proliferation and migration of colon cancer cells. It has been reported that cPA shows several biological activities not shown by LPA. However, understanding of the detailed molecular and cellular mechanism underlying the regulation of the cell cycle by cPA is still in its infancy. In this study, we investigated the effect of cPA treatment on human DLD-1 colon cancer cells by analyzing cell cycle dynamics, gene expression, and AKT phosphorylation. Our findings indicate that cPA inhibits cell cycle progression in DLD-1 colon cancer cells via the downregulation of cyclin D1 and the inhibition of AKT phosphorylation.

Abbreviations

AGP:

alkyl-glycerophosphate

cPA:

cyclic phosphatidic acid

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

fetal bovine serum

LPA:

lysophosphatidic acid

PI3K:

phosphoinositide 3 kinase

SDS:

sodium dodecyl sulfate

siRNA:

small-interfering RNA

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Correspondence to Tamotsu Tsukahara.

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Tsukahara, T., Haniu, H. & Matsuda, Y. Cyclic phosphatidic acid induces G0/G1 arrest, inhibits Akt phosphorylation, and downregulates cyclin D1 expression in colorectal cancer cells. Cell Mol Biol Lett (2014). https://doi.org/10.2478/s11658-014-0224-2

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  • DOI: https://doi.org/10.2478/s11658-014-0224-2

Keywords

  • Cyclic phosphatidic acid
  • Lysophosphatidic acid
  • Alkylglycerophosphate
  • Colon cancer cells
  • Cell cycle analysis
  • Cell proliferation
  • Cyclin D1
  • Akt phosphorylation
  • siRNA
  • Cancer treatment