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

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).

• Authors: Zhao-fei Chen, Jing-yuan Fang, Yu-rong Weng, Dan-feng Sun, Xia Wang, Rong Lu
• Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] (Zhonghua Zhong Liu Za Zhi) Vol. 28 Issue 8 Pg. 564-7 (Aug 2006) ISSN: 0253-3766 [Print] China
• PMID: 17236547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Acetophenones (pharmacology)
• Adenomatous Polyposis Coli Protein (genetics)
• Benzopyrans (pharmacology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (genetics, metabolism, 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, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)