Anticancer activity of chemically prepared shrimp low molecular weight chitin evaluation with the human monocyte leukaemia cell line, THP-1

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Abstract

In the present study, anticancer activities of chitin, chitosan and low molecular weight chitin were evaluated using a human tumour cell line, THP-1. A molecular weight–activity relationship and an electrostatic interaction–activity relationship were determined. The cytotoxic effects of chitin and derivatives were also evaluated using a normal human foetal lung fibroblastic cell line, MRC-5 and the specific cytotoxicity of chitin and derivatives to tumour cell lines was demonstrated. The high antitumour effect of low molecular weight of chitin was established.

Highlights

Anticancer activities of chitin, chitosan and low molecular weight chitin were evaluated. ► Molecular weight–activity relationship was determined. ► High antitumour effect of low molecular weight of chitin was established. ► Low molecular weight chitin has promising roles in natural cancer prevention and treatment.

Introduction

Chitin is a linear polysaccharide joined by β-(1,4)-linked N-acetylglucosamine (GlcNAc) units [1]. It is the second most abundant natural polymer after cellulose [2]. Their unique properties, biodegradability, biocompatibility and non-toxicity, make them useful for a wide range of applications. Although chitin has very strong functional properties in many areas, the water-insoluble property of α-chitin is disadvantageous for its wide application [3]. In the research field of chitin, functional property has been developed for pharmaceutical and new drug candidate [4], [5]. Cytotoxic drugs continue to play a major role in cancer therapy [6]. However, cytotoxic drugs produce side effects, especially the destruction of lymphoid and bone marrow cells. Therefore, strategic improvements in cancer therapy are needed to ameliorate efficiency while decreasing side effects. Most biological activities of chitin are attributed to their free amino groups [7]. Chemical modification of chitin is difficult in general, because chitin is a highly crystalline material with a strongly hydrogen-bonded network structure [8], [9]. The purpose of this work is the determination of the anticancer activities of chitin, chitosan and low molecular weight chitin using a human tumour cell line, THP-1. A molecular weight–activity relationship and an electrostatic interaction–activity relationship were evaluated. The cytotoxic effects of chitin and derivatives were also treated using a normal human foetal lung fibroblastic cell line, MRC-5 and the specific cytotoxicity of chitin and derivatives to tumour cell lines was studied. The function of YKL-40 glycoprotein was also investigated.

Section snippets

Materials and methods

All chemicals used in this study were analytical grade and purchased from Sigma Chemical Co. (St. Louis, MO).

Results

Synthesis of chitin, chitosan and low molecular weight chitin was confirmed by FT-IR data as follows (Fig. 1).

Deacetylation of chitin to produce chitosan was recognized by increasing of NH2 functional groups (708.7 cm−1, 1572.4 cm−1 and 3111.7 cm−1) and by decreasing of Cdouble bondO functional groups (1661.7 cm−1) (Fig. 1a and b).

Chitin hydrolysis was established by similarities of chitin characteristics picks. There is also deacetylation, caused by high concentrations of HCl, and confirmed by decreasing of

Discussion

Synthesis of chitin, chitosan and low molecular weight chitin was confirmed by FT-IR data (Fig. 1).

The cytotoxic effects of chitin, chitosan and low molecular weight chitin on a human normal foetal lung fibroblastic cell line, MRC-5 have been evaluated. The results (Fig. 4) indicate that chitin, chitosan and low molecular weight chitin exhibited no cytotoxic effects at concentrations inferior or equal to 2000 μg/ml. Same results, but with others chitin derivatives, have been cited in literature.

Conclusion

Low molecular weight chitin is an attractive target for selective anticancer drug development. In fact, low molecular weight chitin prepared from the white shrimp P. longirostris (Lucas, 1846) showed a great and specific anticancer effect on the human monocytic leukaemia cell line, THP-1. A molecular weight–activity relationship and an electrostatic interaction-activity relationship were suggested. Also, we speculate that antiapoptic effect of YKL-40 glycoprotein is inhibiting when low

Conflict of interest

The authors do not have any conflicts of interest to report with for this manuscript.

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      It was found that shrimp shell chitin (338 kDa), chitosan (12 kDa) and low Mw chitin (2480 Da) had anti-cancer effects on the human monocytic leukemia cell line (THP-1), meanwhile the IC50 of low Mw chitin (1 μg/mL) was significantly lower than high Mw chitin (739 μg/mL) and chitosan (531 μg/mL). This was speculated that lower Mw had a greater affinity of YKL-40 (a glycoprotein that could bind onto chitin with antiinflammation ability) induced by the steric gene (Salah et al., 2013). Two kinds of N-acetyl chito-oligosaccharides (NA-COS) with Mw of 1–3 kDa and below 1 kDa were prepared from crab shell chitin, both of which displayed an inhibitory effect against protein and DNA oxidation without cytotoxicity, especially compared with NA-COS < 1 kDa, 1–3 kDa NA-COS demonstrated a higher antioxidant ability because of its easy accessibility to incorporate into cells and donate proton (Ngo et al., 2009).

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