In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs

Bishoy Y.A. El-Aarag, Tomonari Kasai, Magdy A.H. Zahran, Nadia I. Zakhary, Tsukasa Shigehiro, Sreeja C. Sekhar, Hussein S. Agwa, Akifumi Mizutani, Hiroshi Murakami, Hiroki Kakuta, Masaharu Seno

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100 μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.

Original languageEnglish
Pages (from-to)283-292
Number of pages10
JournalInternational Immunopharmacology
Volume21
Issue number2
DOIs
Publication statusPublished - Aug 2014

Keywords

  • Angiogenesis
  • Migration
  • NO
  • Thalidomide dithiocarbamate analogs
  • VEGF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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