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

Chang,Pei-Ying; Peng,Shu-Fen; Lee,Chao-Ying; Lu,Chi-Cheng; Tsai,Shih-Chang; Shieh,Tzong-Ming; Wu,Tian-Shung; Tu,Ming-Gene; Chen,Michael Yuanchien; Yang,Jai-Sing

doi:10.3892/ijo.2013.2050

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

Authors:
- Pei-Ying Chang
- Shu-Fen Peng
- Chao-Ying Lee
- Chi-Cheng Lu
- Shih-Chang Tsai
- Tzong-Ming Shieh
- Tian-Shung Wu
- Ming-Gene Tu
- Michael Yuanchien Chen
- Jai-Sing Yang
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Affiliations: Department of Dentistry, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C., School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Pharmacology, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Dental Hygiene, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, R.O.C., Dental Department and Division of Oral Maxillofacial Surgery, China Medical University Hospital, Taichung 40447, Taiwan, R.O.C.
Published online on: August 5, 2013 https://doi.org/10.3892/ijo.2013.2050
Pages: 1141-1150

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Abstract

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.

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