Organoselenium compounds as novel adjuvants of chemotherapy drugs—a promising approach to fight cancer drug resistance

Gabriella Spengler, Márió Gajdács, Małgorzata Anna Marć, Enrique Domínguez-Álvarez, Carmen Sanmartín

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Malignant diseases present a serious public health burden and their treatment with traditional chemotherapy cannot be considered an all-round solution, due to toxic side effects. Selenium compounds (Se-compounds) have received substantial attention in medicinal chemistry, especially in experimental chemotherapy, both as cytotoxic agents and adjuvants in chemotherapy. A checkerboard microplate method was applied to study the drug interactions of Se-compounds and clinically relevant chemotherapeutic drugs against the multidrug-resistant (MDR) subtype of mouse T-lymphoma cells overexpressing the ABCB1 transporter. Se-compounds showed synergistic interactions with chemotherapeutic agents targeting the topoisomerase enzymes or the microtubule apparatus. The ketone-containing selenoesters showed synergism at lower concentrations (1.25 µM). Most of the tested compounds interacted antagonistically with alkylating agents and verapamil. A thiophene-containing Se-compound showed synergism with all tested drugs, except cisplatin. While the exact mechanism of drug interactions is yet unknown, the potency of the selenocompounds as efflux pump inhibitors or the potentiation of their efficacy as reactive oxygen species modulators may play a role in their complementary activity against the tested MDR lymphoma cell line.

Original languageEnglish
Article number336
JournalMolecules
Volume24
Issue number2
DOIs
Publication statusPublished - Jan 18 2019

Keywords

  • Anticancer
  • Checkerboard
  • Combination
  • Doxorubicin
  • Lymphoma
  • Selenium
  • Topotecan

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Organoselenium compounds as novel adjuvants of chemotherapy drugs—a promising approach to fight cancer drug resistance'. Together they form a unique fingerprint.

  • Cite this