Effect of the association of 1-methyl-DL-tryptophan with paclitaxel on the expression of indoleamine 2,3-dioxygenase in cultured cancer cells from patients with breast cancer

Med Oncol. 2015 Nov;32(11):248. doi: 10.1007/s12032-015-0694-8. Epub 2015 Oct 6.

Abstract

Breast cancer is the most common type of cancer among women and the survival of patients affected by it is increasing, mainly due to several new approaches in early diagnosis and more effective treatments. The enzyme indoleamine 2,3-dioxygenase (IDO) is expressed in many cells, including tumor cells. IDO acts by inhibiting the proliferation of T lymphocytes, thus compromising their cytotoxic activity. 1-Methyl-DL-tryptophan (1MT) is a competitive inhibitor of IDO, which blocks its immunosuppressive effect. Paclitaxel is an antineoplastic drug largely used in breast cancer therapy. Thus, this study aimed to determine the in vitro effect of the association of 1MT and paclitaxel chemotherapy, as an approach to reduce tumor growth. It is believed that this would allow the restoration of T lymphocyte proliferation capability and its cytotoxic response. The supplemented cultures showed that the most significant differences in the expression of IDO were observed in the group treated with paclitaxel associated with 1-MT continuous supplementation, reducing enzyme expression from 12.06 to 3.56 %. This association was more effective in reducing IDO expression and could collaborate in developing a new therapeutic strategy for breast cancer treatment.

Keywords: Cancer-associated therapy; Flow cytometry; IDO; In vitro treatment; Taxol®; Tryptophan catabolism.

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Breast Neoplasms / enzymology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Paclitaxel / administration & dosage*
  • Tryptophan / administration & dosage
  • Tryptophan / analogs & derivatives*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Tryptophan
  • Paclitaxel
  • 1-methyltryptophan