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Octahedral Pt(IV) complex K101 induces apoptosis via ERK1/2 activation and the p53 pathway in human colon cancer cells.

Abstract
Recently, the synthesized octahedral Pt(IV) compound trans,cis-Pt(acetato)2Cl2(1,4-butanediamine), K101, showed potent anti-tumor activity in vitro and in vivo. For the further investigation of K101-induced anti-cancer activity, we tested cytotoxicity against various cancer cell lines and performed the histoculture drug response assay (HDRA) against human colorectal tumor tissues in vitro. We investigated the signaling pathway of K101-induced apoptosis via expression of p53 and ERK1/2 in the human colon cell line HCT116. The cytotoxicity and the three-dimensional HDRA of K101 were evaluated using the MTT assay. To study the K101-induced apoptosis pathway, we performed FACS analysis and immunoblotting of p53, p21, Bax, Fas and ERK1/2 in HCT116 cells treated with or without K101. The cytotoxic IC50 values of K101 ranged from 1.15 to 2.38 micromol/l, compared to cisplatin ranging from 2.13 to 13.1 micromol/l. Among several cancer cell lines, K101 showed greater potency than cisplatin in colon cancer cell lines. In the HDRA, K101 showed 80.0-91.4% efficacy rates compared with 48.6% for cisplatin against colorectal cancer patient tissues. In the signaling pathway, the expression of p53 and phospho-ERK1/2 was increased in a time-dependent manner by treatment with K101 in the HCT116 cells. When K101 was treated with MEK inhibitor U0126, the cell death rate was increased. The octahedral Pt(IV) complex K101 could be an attractive candidate as a chemotherapeutic agent against colon cancer. ERK1/2 activation and the p53 pathway may play significant functions in mediating K101-induced apoptosis in human colon cancer cells.
AuthorsYoung-Ee Kwon, Kuk-Hwan Kim
JournalAnti-cancer drugs (Anticancer Drugs) Vol. 17 Issue 5 Pg. 553-8 (Jun 2006) ISSN: 0959-4973 [Print] England
PMID16702812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Butadienes
  • K101 compound
  • Nitriles
  • Organoplatinum Compounds
  • Tumor Suppressor Protein p53
  • U 0126
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
Topics
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Butadienes (pharmacology)
  • Cell Line, Tumor
  • Colonic Neoplasms (drug therapy, metabolism, pathology)
  • Enzyme Activation (drug effects)
  • Humans
  • Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
  • Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
  • Nitriles (pharmacology)
  • Organoplatinum Compounds (pharmacology)
  • Signal Transduction (drug effects)
  • Tumor Suppressor Protein p53 (metabolism)

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