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

AI Article Synopsis

  • Inhibition of angiogenesis is being explored as a promising cancer treatment, with thalidomide sparking renewed research despite its teratogenic effects.
  • The study examined two thalidomide dithiocarbamate analogs' impact on human breast cancer cells and endothelial cells, looking at their effects on cell growth and key inflammatory factors.
  • Results showed that while thalidomide itself had little impact, the analogs effectively reduced cell proliferation and angiogenesis while also suppressing the expression of important growth and inflammatory proteins, highlighting their potential in cancer treatment.

Article 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 6.25-100μM. 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.

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http://dx.doi.org/10.1016/j.intimp.2014.05.007DOI Listing

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