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 - 2014

Fingerprint

Thalidomide
Human Umbilical Vein Endothelial Cells
Matrix Metalloproteinases
Interleukin-8
Wound Healing
Interleukin-6
Nitric Oxide
In Vitro Techniques
Neoplasms
Breast Neoplasms
Cell Line
Research

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology
  • Medicine(all)

Cite this

In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs. / El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I.; Shigehiro, Tsukasa; Sekhar, Sreeja C.; Agwa, Hussein S.; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu.

In: International Immunopharmacology, Vol. 21, No. 2, 2014, p. 283-292.

Research output: Contribution to journalArticle

El-Aarag, Bishoy Y A ; Kasai, Tomonari ; Zahran, Magdy A H ; Zakhary, Nadia I. ; Shigehiro, Tsukasa ; Sekhar, Sreeja C. ; Agwa, Hussein S. ; Mizutani, Akifumi ; Murakami, Hiroshi ; Kakuta, Hiroki ; Seno, Masaharu. / In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs. In: International Immunopharmacology. 2014 ; Vol. 21, No. 2. pp. 283-292.
@article{dca6ba2c30ce4bd19610dfe6ce49fa63,
title = "In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs",
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.",
keywords = "Angiogenesis, Migration, NO, Thalidomide dithiocarbamate analogs, VEGF",
author = "El-Aarag, {Bishoy Y A} and Tomonari Kasai and Zahran, {Magdy A H} and Zakhary, {Nadia I.} and Tsukasa Shigehiro and Sekhar, {Sreeja C.} and Agwa, {Hussein S.} and Akifumi Mizutani and Hiroshi Murakami and Hiroki Kakuta and Masaharu Seno",
year = "2014",
doi = "10.1016/j.intimp.2014.05.007",
language = "English",
volume = "21",
pages = "283--292",
journal = "International Immunopharmacology",
issn = "1567-5769",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs

AU - El-Aarag, Bishoy Y A

AU - Kasai, Tomonari

AU - Zahran, Magdy A H

AU - Zakhary, Nadia I.

AU - Shigehiro, Tsukasa

AU - Sekhar, Sreeja C.

AU - Agwa, Hussein S.

AU - Mizutani, Akifumi

AU - Murakami, Hiroshi

AU - Kakuta, Hiroki

AU - Seno, Masaharu

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Migration

KW - NO

KW - Thalidomide dithiocarbamate analogs

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=84901985608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901985608&partnerID=8YFLogxK

U2 - 10.1016/j.intimp.2014.05.007

DO - 10.1016/j.intimp.2014.05.007

M3 - Article

C2 - 24859059

AN - SCOPUS:84901985608

VL - 21

SP - 283

EP - 292

JO - International Immunopharmacology

JF - International Immunopharmacology

SN - 1567-5769

IS - 2

ER -