title: Novel FTS-diamine/cinnamic acid hybrids inhibit tumor cell proliferation and migration and promote apoptosis via blocking Ras-related signaling in vitro.
abstract: Novel FTS-diamine/cinnamic acid hybrids 7a-f were prepared, and their in vitro biological activities were evaluated. It was found that 7c showed the strongest anti-proliferation activities against cancer cells in vitro and significant growth inhibition of tumor in vivo, and more potential for inhibitory selectivity to tumor cells than intermediate 6 and FTS. Furthermore, the anti-proliferative effect of 7c in Lovo cell lines followed a similar pattern, which included a dose-dependent induction of cell apoptosis via the up-regulation of Bax as well as activated caspase-3 and down-regulation of Bcl-2, and the inhibition of cancer cells migration and invasion in a concentration-dependent way. More importantly, 7c could significantly block Ras-related signaling pathways, which may contribute to its pro-apoptotic induction of the cancer cell lines and its inhibition of carcinoma cell proliferation, migration, and invasion. Therefore, our novel findings may provide a new framework for the discovery of new FTS hybrids for the intervention of human carcinoma cells.
authors.affiliation: School of Pharmacy, Nantong University, Nantong, 226001, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ling
authors.forename: Xinmei
authors.initials: X
authors.lastname: Zhao
authors.forename: Xianghua
authors.initials: X
authors.lastname: Li
authors.forename: Xuemin
authors.initials: X
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005204:Farnesol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011905:Genes, ras / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000188:drug therapy; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; D012459:Salicylates; C093323:farnesylthiosalicylic acid; C029010:cinnamic acid; D005204:Farnesol