title: Anticancer effects of novel thalidomide analogs in A549 cells through inhibition of vascular endothelial growth factor and matrix metalloproteinase-2.
abstract: Lung cancer is one of the major causes of cancer-related mortality worldwide, and non-small-cell lung cancer is the most common form of lung cancer. Several studies had shown that thalidomide has potential for prevention and therapy of cancer. Therefore, the current study aimed to investigate the antitumor effects of two novel thalidomide analogs in human lung cancer A549 cells. The antiproliferative, antimigratory, and apoptotic effects in A549 cells induced by thalidomide analogs were examined. In addition, their effects on the expression of mRNAs encoding vascular endothelial growth factor165 (VEGF165) and matrix metalloproteinase-2 (MMP-2) were evaluated. Their influence on the tumor volume in nude mice was also determined. Results revealed that thalidomide analogs exhibited antiproliferative, antimigratory, and apoptotic activities with more pronounced effect than thalidomide drug. Furthermore, analogs 1 and 2 suppressed the expression levels of VEGF165 by 42% and 53.2% and those of MMP-2 by 45% and 52%, respectively. Thalidomide analogs 1 and 2 also reduced the tumor volume by 30.11% and 53.52%, respectively. Therefore, this study provides evidence that thalidomide analogs may serve as a new therapeutic option for treating lung cancer.
authors.affiliation: Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom, Egypt; Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan. Electronic address: bishoy.yousef@gmail.com.
authors.forename: Bishoy
authors.initials: B
authors.lastname: El-Aarag
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Kasai
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Masuda
authors.affiliation: Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom, Egypt.
authors.forename: Hussein
authors.initials: H
authors.lastname: Agwa
authors.affiliation: Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom, Egypt.
authors.forename: Magdy
authors.initials: M
authors.lastname: Zahran
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Seno
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D020778:Matrix Metalloproteinase 2
keywords: A549 cancer cells; Anticancer; MMP-2; Thalidomide analogs; VEGF