Dextran-Catechin Conjugate: A Potential Treatment Against the Pancreatic Ductal Adenocarcinoma

被引:78
|
作者
Vittorio, Orazio [1 ,2 ,3 ]
Cirillo, Giuseppe [4 ]
Iemma, Francesca [1 ,4 ]
Di Turi, Giovanni [5 ]
Jacchetti, Emanuela [2 ,3 ]
Curcio, Michele [6 ]
Barbuti, Serena [6 ]
Funel, Niccola [5 ]
Parisi, Ortensia Ilaria [1 ,4 ]
Puoci, Francesco [1 ,4 ]
Picci, Nevio [1 ,4 ]
机构
[1] Univ Calabria, Dept Pharmaceut Sci, I-87036 Arcavacata Di Rende, CS, Italy
[2] NEST Scuola Normale Super, I-56126 Pisa, Italy
[3] CNR, Ist Nanosci, I-56100 Pisa, Italy
[4] Univ Calabria, Macrofarm Srl, I-87036 Arcavacata Di Rende, CS, Italy
[5] Univ Pisa, Dept Oncol Transplantat & Adv Technol Med, I-56100 Pisa, Italy
[6] Cisanello Hosp, Immunohematol Unit, I-56100 Pisa, Italy
关键词
anticancer activity; antioxidant-polymer conjugates; catechin; pancreatic ductal adenocarcinoma; polymeric drugs; GALLIC ACID; TEA POLYPHENOLS; GREEN TEA; CANCER; GEMCITABINE; DRUG; INHIBITION; 24-HOUR; GROWTH;
D O I
10.1007/s11095-012-0790-9
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC). The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR and GPC analyses, while the functionalization degree was determined by the Folin-Ciocalteu assay. The biological activity of the catechin-dextran conjugate was tested on two different cell lines derived from human pancreatic cancer (MIA PaCa-2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing cells evaluated. Both the cancer cell lines are killed when exposed to the conjugate, and undergo apoptosis after the incubation with catechin-dextran which resulted more effective in killing pancreatic tumor cells compared to the catechin alone. Moreover, our experimental data indicate that the conjugate was less cytotoxic to human pancreatic nestin-expressing cells which are considered a good model of non-neoplastic pancreatic cells. The suitability of newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved confirming the high potential application of the proposed macromolecula system in the cancer therapy.
引用
收藏
页码:2601 / 2614
页数:14
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