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
N1 - Funding Information:
The authors appreciate Ms. Mami Asakura for the excellent assistance throughout the whole study. This study was partly supported by Grant-in-Aid for Challenging Exploratory Research no. 23650598 and Grant-in-Aid for Scientific Research (A) no. 25242045 and (C) nos. 24501315 and 24510151 . The authors alone are responsible for the content and writing of the manuscript.
PY - 2014/8
Y1 - 2014/8
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
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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
SN - 1567-5769
VL - 21
SP - 283
EP - 292
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 2
ER -
