Induction of Permeability and Apoptosis in Colon Cancer Cell Line with Chitosan

以甲殼素誘導大腸癌細胞滲透作用和細胞凋亡

Zakir Hossain ； Koretaro Takahashi

《藥物食品分析》 16卷5期 (2008/10) Pp. 1-8

摘要

本研究以甲殼素作用在大腸癌細胞(Caco-2)之單層細胞緊密連接(TJs)處爲研究模型，研究同時發現低分子量水溶性甲殼素(LMWC)對HT-29細胞產生細胞凋亡。以lucifer yellow可評估甲殼素對Caco-2單層細胞產生阻隔特性改變，包括transepithelial electrical resistance (Teer)和滲透性的改變。高分子量甲殼素(HMWC)被發現在低濃度有高達50%的劑量依賴性可降低Teer對Caco-2單層細胞損害，以0.001-0.0001% HMWC作用120分鐘和對照組比較，證實HMWC在TJs增加lucifer yellow的通透性。結果顯示，HMWC不影響細胞骨架之F-肌動蛋白。LMWC被證明可誘導細胞凋亡使DNA功能碎裂作爲一抗腫瘤化合物。本研究結果顯示HMWC可作爲細胞內藥物釋放建議物質且LMWC作用在大腸癌治療具有潛在價值。

關鍵字

甲殼素 ； Caco-2細胞 ； HT-29細胞 ； F-actin ； 緊密連接 ； 細胞凋亡

並列摘要

The effect of chitosan on tight junctions (TJs) permeability on Caco-2 cell monolayer intestinal model was investigated. We have also investigated the effects of low molecular weight water-soluble chitosan (LMWC) on apoptosis in HT-29 cell. The changes in barrier properties of Caco-2 cell monolayers, including transepithelial electrical resistance (TEER) and permeability to Lucifer yellow, were assessed in response to chitosan treatment. High molecular weight chitosan (HMWC) was found to cause up to 50% dose-dependent reduction in TEER of Caco-2 cell monolayer without damage to the cell membrane under lower concentration. The effect of HMWC on TJs was confirmed by increased permeability of lucifer yellow when cells were treated with 0.001-0.0001% HMWC for 120 min compared to control cells. Results showed that HMWC did not affect the F-actin of cytoskeleton. LMWC was proven to be an antitumor compound as shown by inducing apoptosis as a function of DNA fragmentation. These results suggest that HMWC is an useful drug delivery agent in paracellular pathway and LMWC has potential value in colon cancer therapy.

並列關鍵字

Chitosan ； Caco-2 cells ； HT-29 cells ； F-actin ； tight junction ； apoptosis