[The effect of PKC-delta inhibitor Rottlerin on human colon cancer cell line SW1116 and its mechanism]

Zhonghua Zhong Liu Za Zhi. 2006 Aug;28(8):564-7.
[Article in Chinese]

Abstract

Objective: To evaluate the effect of PKC-delta inhibitor Rottlerin on human colon cancer cells and its mechanism.

Methods: Human colon cancer cell line SW1116 cells were treated with Rottlerin. The transcriptional level of DNA methyltransferase (Dnmt)1, Dnmt3a and Dnmt3b was detected by real-time RT-PCR. Cell cycle distribution was evaluated by flow cytometry (FCM). In addition, cellular morphological changes were examined by light microscopy.

Results: PKC-delta inhibitor decreased the expression of Dnmt1, Dnmt3a mRNA, up-regulated APC, p21(WAF1) and p16(INK4A) mRNA. Demonstarted by flow cytometry, Rottlerin increased the percentage of cell cycle G0/G1 phase cell numbers (P = 0.02) and decreased the percentage of cell cycle G2/M phase cell numbers (P = 0.01). Remarkable changes of cellular morphology were observed under light microscope: The volume and cytoplasm of cells treated with Rottlerin were increased. The cell contour was not very clear, and mitotic figures were less frequently seen.

Conclusion: PKC-delta inhibitor Rottlerin inhibites cell division and proliferation of the colon cancer SW1116 cells through regulating DNA methylation and blocking the signaling pathway of mitogen-activated protein kinase (MAPK).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology*
  • Adenomatous Polyposis Coli Protein / genetics
  • Benzopyrans / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methyltransferase 3A
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Protein Kinase C-delta / antagonists & inhibitors*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects

Substances

  • Acetophenones
  • Adenomatous Polyposis Coli Protein
  • Benzopyrans
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNMT3A protein, human
  • RNA, Messenger
  • rottlerin
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • DNMT1 protein, human
  • Protein Kinase C-delta