New Chalcone Derivative Inhibits ABCB1 in Multidrug Resistant T-cell Lymphoma and Colon Adenocarcinoma Cells

Anticancer Res. 2019 Dec;39(12):6499-6505. doi: 10.21873/anticanres.13864.

Abstract

Background/aim: Development of new potential drugs to overcome multidrug resistance to chemotherapy is a big challenge for cancer treatment. Attention is also given to the natural compounds and their derivatives. The study aimed at evaluating the impact of a new chalcone derivative (1C) on multidrug resistant cell lines, focusing on P-glycoprotein (P-gp, ABCB1) inhibition, as well as 1C-doxorubicin interaction in vitro.

Materials and methods: Cytotoxic and antiproliferative effects of the 1C compound were assessed by thiazolyl blue tetrazolium bromide (MTT) method in mouse T-cell lymphoma and human colon adenocarcinoma cells expressing ABCB1. Alterations in ABCB1 activity were evaluated by rhodamine 123 accumulation assay using flow cytometry. Drug-drug interaction was studied using combination assay.

Results: Our results confirmed antiproliferative, cytotoxic, as well as ABCB1 inhibitory potential of 1C in both tested ABCB1-expressing cancer cell lines. Furthermore, 1C displayed synergistic interaction with doxorubicin.

Conclusion: Our results suggest the 1C chalcone derivative as a promising compound against resistant lymphoma and colon cancer, which could be used in monotherapy or in combination with other chemotherapeutics.

Keywords: ABCB1; Chalcone; P-glycoprotein; T-lymphoma; colon adenocarcinoma; doxorubicin.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chalcones / pharmacology*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism*
  • Down-Regulation
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lymphoma, T-Cell / drug therapy
  • Lymphoma, T-Cell / metabolism*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Chalcones
  • Doxorubicin