Curcumin-loaded nanoparticles induce apoptotic cell death through regulation of the function of MDR1 and reactive oxygen species in cisplatin-resistant CAR human oral cancer cells

被引:111
作者
Chang, Pei-Ying [1 ,6 ,7 ]
Peng, Shu-Fen [2 ]
Lee, Chao-Ying [5 ]
Lu, Chi-Cheng [4 ]
Tsai, Shih-Chang [2 ]
Shieh, Tzong-Ming [3 ]
Wu, Tian-Shung [8 ]
Tu, Ming-Gene [1 ,6 ,7 ]
Chen, Michael Yuanchien [1 ,6 ,7 ]
Yang, Jai-Sing
机构
[1] China Med Univ, Dept Dent, Taichung 404, Taiwan
[2] China Med Univ, Dept Biol Sci & Technol, Taichung 404, Taiwan
[3] China Med Univ, Dept Dent Hyg, Taichung 404, Taiwan
[4] China Med Univ, Dept Pharmacol, Taichung 404, Taiwan
[5] China Med Univ, Sch Pharm, Taichung 404, Taiwan
[6] China Med Univ Hosp, Dept Dent, Taichung 404, Taiwan
[7] China Med Univ Hosp, Div Oral Maxillofacial Surg, Taichung 404, Taiwan
[8] Natl Cheng Kung Univ, Dept Chem, Tainan 701, Taiwan
关键词
curcumin nanoparticles; apoptosis; multiple drug resistance 1; reactive oxygen species; CAL27-cisplatin resistant human oral cancer cells; PLGA NANOPARTICLES; MULTIDRUG-RESISTANCE; NECK-CANCER; IN-VITRO; MOLECULAR-MECHANISMS; P-GLYCOPROTEIN; BIOAVAILABILITY; HEAD; DESIGN; AUTOPHAGY;
D O I
10.3892/ijo.2013.2050
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Curcumin is a polyphenolic compound which possesses anticancer potential. It has been shown to induce cell death in a variety of cancer cells, however, its effect on CAL27-cisplatin-resistant human oral cancer cells (CAR cells) has not been elucidated to date. The low water solubility of curcumin which leads to poor bioavailability, however, has been highlighted as a major limiting factor. In this study, we utilized water-soluble PLGA curcumin nanoparticles (Cur-NPs), and investigated the effects of Cur-NPs on CAR cells. The results showed Cur-NPs induced apoptosis in CAR cells but exhibited low cytotoxicity to normal human gingival fibroblasts (HGFs) and normal human oral keratinocytes (OKs). Cur-NPs triggered DNA concentration, fragmentation and subsequent apoptosis. Compared to untreated CAR cells, a more detectable amount of Calcein-AM accumulation was found inside the treated CAR cells. Cur-NPs suppressed the protein and mRNA expression levels of MDR1. Both the activity and the expression levels of caspase-3 and caspase-9 were elevated in the treated CAR cells. The Cur-NP-triggered apoptosis was blocked by specific inhibitors of pan-caspase (z-VAD-fmk), caspase-3 (z-DEVD-fmk), caspase-9 (z-LEHD-fmk) and antioxidant agent (N-acetylcysteine; NAC). Cur-NPs increased reactive oxygen species (ROS) production, upregulated the protein expression levels of cleaved caspase-3/caspase-9, cytochrome c, Apaf-1, AIF, Bax and downregulated the protein levels of Bcl-2. Our results suggest that Cur-NPs triggered the intrinsic apoptotic pathway through regulating the function of multiple drug resistance protein 1 (MDR1) and the production of reactive oxygen species (ROS) in CAR cells. Cur-NPs could be potentially efficacious in the treatment of cisplatin-resistant human oral cancer.
引用
收藏
页码:1141 / 1150
页数:10
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