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壳聚糖通过诱导口腔癌细胞凋亡和细胞周期停滞发挥抗癌活性。

Chitosan exerts anticancer activity through induction of apoptosis and cell cycle arrest in oral cancer cells.

作者信息

Wimardhani Yuniardini S, Suniarti Dewi F, Freisleben Hans J, Wanandi Septelia I, Siregar Nurjati C, Ikeda Masa-Aki

机构信息

Graduate Study Program in Biomedical Science, Faculty of Medicine, University of Indonesia.

出版信息

J Oral Sci. 2014 Jun;56(2):119-26. doi: 10.2334/josnusd.56.119.

DOI:10.2334/josnusd.56.119
PMID:24930748
Abstract

Chitosan, a multipurpose biomaterial, has been shown to exert effects against several types of cancer including oral cancer. However, the mechanisms underlying the anticancer activities of chitosan on oral squamous cell carcinoma (SCC) cells remain largely unknown. The present study aimed to compare the effects of low-molecular-weight chitosan (LMWC) and cisplatin on oral SCC Ca9-22 and non-cancer keratinocyte HaCaT cell lines. Cell viability and cell cycle profiles were measured by MTT assay and laser scanning cytometry, respectively. Apoptosis was examined by TUNEL assay and electron microscopy, followed by analysis of caspase activity. LMWC exhibited cytotoxic effects on Ca9-22, but not HaCaT cells, whereas cisplatin induced apoptosis in both types of cells. Exposure of Ca9-22 cells to LMWC led to G1/S cell cycle arrest and an increase of TUNEL-positive cells accompanied by an early apoptotic cell morphology and subtle increases of caspase activity. Short-term LMWC exposure was less cytotoxic to HaCaT cells than to Ca9-22 cells, and anticancer activity was exerted through induction of apoptosis and cell cycle arrest, suggesting that LMWC could be a promising natural anticancer agent with fewer side effects on normal cells.

摘要

壳聚糖是一种多功能生物材料,已被证明对包括口腔癌在内的多种癌症具有抑制作用。然而,壳聚糖对口腔鳞状细胞癌(SCC)细胞抗癌活性的潜在机制仍 largely 未知。本研究旨在比较低分子量壳聚糖(LMWC)和顺铂对口腔 SCC Ca9-22 细胞系和非癌角质形成细胞 HaCaT 细胞系的影响。分别通过 MTT 法和激光扫描细胞术测量细胞活力和细胞周期分布。通过 TUNEL 法和电子显微镜检查细胞凋亡,随后分析 caspase 活性。LMWC 对 Ca9-22 细胞具有细胞毒性作用,但对 HaCaT 细胞无此作用,而顺铂可诱导两种类型细胞凋亡。将 Ca9-22 细胞暴露于 LMWC 导致 G1/S 期细胞周期阻滞以及 TUNEL 阳性细胞增加,同时伴有早期凋亡细胞形态和 caspase 活性的轻微增加。短期暴露于 LMWC 对 HaCaT 细胞的细胞毒性低于对 Ca9-22 细胞的毒性,其抗癌活性是通过诱导细胞凋亡和细胞周期阻滞来实现的,这表明 LMWC 可能是一种有前景的天然抗癌剂,对正常细胞的副作用较少。

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