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.

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.

• 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
• Journal: International journal of oncology (Int J Oncol) Vol. 43 Issue 4 Pg. 1141-50 (Oct 2013) ISSN: 1791-2423 [Electronic] Greece
• PMID: 23917396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Reactive Oxygen Species
• Curcumin
• Cisplatin

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis, genetics)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin (therapeutic use)
• Curcumin (administration & dosage, chemistry)
• Drug Resistance, Neoplasm (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mouth Neoplasms (drug therapy, genetics, pathology)
• Nanoparticles (administration & dosage, chemistry)
• Reactive Oxygen Species (metabolism)