Carbohydrate Polymers 87 (2012) 1383–1389 Contents lists available at SciVerse ScienceDirect Carbohydrate Polymers jo u rn al hom epa ge: www.elsevier.com/locate/carbpol Aminoethylated chitooligomers and their apoptotic activity on AGS human cancer cells Mustafa Zafer Karagozlu a , Fatih Karadeniz a , Chang-Suk Kong b , Se-Kwon Kim a,c,∗ a Department of Chemistry, Pukyong National University, Busan 608-737, South Korea b Department of Food and Nutrition, College of Medical and Life Science, Silla University, Busan 617-736, South Korea c Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, South Korea a r t i c l e i n f o Article history: Received 25 June 2011 Received in revised form 8 September 2011 Accepted 9 September 2011 Available online 16 September 2011 Keywords: Aminoethyl chitooligomers Apoptosis AGS a b s t r a c t In this study, the ability of aminoethylation of chitooligomers (COS) to inhibit the proliferation of AGS human gastric adenocarcinoma cells was evaluated using COS with lower molecular weight (<1 kDa). As water-soluble aminoderivatized COS derivatives, aminoethyl-COS (AE-COS), dimethyl aminoethyl- COS (DMAE-COS) and diethyl aminoethyl-COS (DEAE-COS) were synthesized and confirmed by their IR spectra results in comparison to previous study. Aminoderivatized COS-induced cell death was char- acterized by cell viability, changes in nuclear morphology and cell morphology. All aminoderivatized COS significantly inhibited cell proliferation of AGS cancer cells in a dose-dependent manner. Moreover, protein and gene expression levels of the regulators involved in apoptosis pathway such as Caspase-9, Bax, p53 and p21 were examined using RT-PCR and Western blot analysis. The exposure of synthesized COS derivatives to AGS cells induced apoptotic activity. Therefore, the present results suggest that all aminoderivatized COS derivatives have a promising potential as valuable as cancer chemopreventive agents. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Chitosan, a natural nontoxic heteropolysaccharide composed of -1,4-d-glucosamine and N-acetyl-d-glucosamine has been widely applied in the biomedical and pharmaceutical industries, due to its anti-microbial activity (Jeon, Park, & Kim, 2001; Kong, Kim, Ahn, Byun, & Kim, 2010), anti-viral activity (Artan, Karadeniz, Karagozlu, Kim, & Kim, 2010), antioxidant effect (Park, Je, & Kim, 2004) and anti-diabetic value (Karadeniz, Artan, Kim, & Kim, 2008) and anti-cancer significance (Kim & Rajapakse, 2005). Recent stud- ies on chitosan have shown that there is interest in converting it into soluble chitooligomers (COS) obtained by either chemical depolymerization (Defaye & Guillot, 1994; Horowitz, Roseman, & Blumenthal, 1957; Tsukada & Inoue, 1981) or enzymatic hydrolysis of chitosan (Izume & Ohtakara, 1987; Muzzarelli, 2010; Muzzarelli, Stanic, & Ramos, 1999; Muzzarelli, Terbojevuch, Muzarelli, & Francescangeli, 2002; Muzzarelli, Tomasetti, & Ilari, 1994). The lowest oligomers of chitosan are not only water-soluble but are also even more versatile than chitosan (Qin, Du, Xiao, Li, & Gao, 2002). ∗ Corresponding author at: Department of Chemistry, Pukyong National Univer- sity, Busan 608-737, South Korea. Tel.: +82 51 629 7094; fax: +82 51 629 7099. E-mail address: sknkim@pknu.ac.kr (S.-K. Kim). Apoptosis is the principal form of programmed cell death, contributes to the development and the proper functioning of mul- ticellular organisms through the removal of virus-infected cells and cancer cells (MacFarlane, 2003). Although most of the current anti-cancer therapies rely on the eradication of tumor cells, drugs promoting apoptosis may be effective against many cancers and should become an important strategy to counteract cancer (Fesik, 2005). Gastric cancer is one of the most frequent causes of death: although the incidence and mortality have been decreasing, it is still the second most frequent cause of death around the world, after lung cancer (Lee, Yang, & Ahn, 2002). Sub-types of gastric cancer exist and this classification depends on the tissues where they originate: adenocarcinoma is the most common gastric can- cer, being reported as cause of death in 95% of diagnosed subjects. The AGS cell line is a human gastric adenocarcinoma, widely used as a model system for evaluating cancer cell apoptosis (Liu et al., 2003). In a previous study, water-soluble aminoderivatized COS with medium molecular weight were synthesized with different sub- stituent groups and, new biological activities were evaluated (Karagozlu, Kim, Karadeniz, Kong, & Kim, 2010). Scope of the present study is the enhancement of the ability of aminoethy- lated COS to inhibit adenocarcinoma cell proliferation and to induce apoptosis. 0144-8617/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.carbpol.2011.09.034