Chalcone HTMC causes in vitro selective cytotoxicity, cell-cycle G1 phase arrest through p53-dependent pathway in human lung adenocarcinoma A549 cells, and in vivo tumor growth suppression

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6508-12. doi: 10.1016/j.bmcl.2010.09.056. Epub 2010 Sep 17.

Abstract

The present Letter identified 2'-hydroxy-2,3,4',6'-tetramethoxychalcone (HTMC) as a potent in vitro cytotoxic agent with selective activity against cell lines derived from human lung cancer. In A549 lung adenocarcinoma cells, HTMC caused G1 phase cell-cycle arrest. HTMC treatment also led to an inhibition of cell-cycle regulatory proteins phosphorylation of cdc2 (Tyr(15) and Tyr(161)) and Rb (Ser(795) and Ser(807/811)), which was accompanied by the accumulation of tumor suppressor genes p53 and p21. In addition, in vivo data demonstrated that HTMC act as a tumor growth suppressing agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle Proteins / metabolism
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • G1 Phase / drug effects*
  • Genes, p53*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Phosphorylation

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins