DM-1, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate: a curcumin analog with a synergic effect in combination with paclitaxel in breast cancer treatment

Tumour Biol. 2012 Jun;33(3):775-85. doi: 10.1007/s13277-011-0293-z. Epub 2011 Dec 23.

Abstract

This paper describes a new method for the preparation of sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate, DM-1, and 3-oxo-penta-1,4-dienyl-bis (2-methoxy-phenolate), DM-2. The aim of this work was to evaluate the antitumor effects of DM-1 in adjuvant chemotherapy for breast cancer treatment. Mice bearing mammary adenocarcinomas (Ehrlich ascites tumors) were treated with paclitaxel alone, DM-1 alone, and paclitaxel + DM-1. Tumor samples were used to perform cytological analysis by the Papanicolaou method and apoptosis analysis by annexin V and phosphorylated caspase 3. The paclitaxel + DM-1 group had decreased tumor areas and tumor volumes, and the frequency of metastasis was significantly reduced. This caused a decrease in cachexia, which is usually caused by the tumor. Furthermore, treatment with paclitaxel + DM-1 and DM-1 alone increased the occurrence of apoptosis up to 40% in tumor cells, which is 35% more than in the group treated with paclitaxel alone. This cell death was mainly caused through phosphorylated caspase 3 (11% increase in paclitaxel + DM-1 compared to the paclitaxel group), as confirmed by reduced malignancy criteria in the ascitic fluid. DM-1 emerges as a potential treatment for breast cancer and may act as an adjuvant in chemotherapy, enhancing antitumor drug activity with reduced side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects
  • Female
  • Guaiacol / administration & dosage
  • Guaiacol / analogs & derivatives*
  • Guaiacol / pharmacology
  • Guaiacol / therapeutic use
  • Ketones / administration & dosage
  • Ketones / pharmacology
  • Ketones / therapeutic use*
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / mortality
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis
  • Paclitaxel / administration & dosage
  • Survival Analysis
  • Tumor Burden / drug effects

Substances

  • 4-(5-(4-hydroxy-3-methoxyphenyl)-3-oxopenta-1,4-dienyl)-2-methoxyphenol
  • Ketones
  • Guaiacol
  • Caspase 3
  • Paclitaxel