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
  • View Affiliations

  • 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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October 2013
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APA
Chang, P., Peng, S., Lee, C., Lu, C., Tsai, S., Shieh, T. ... Yang, J. (2013). 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. International Journal of Oncology, 43, 1141-1150. https://doi.org/10.3892/ijo.2013.2050
MLA
Chang, P., Peng, S., Lee, C., Lu, C., Tsai, S., Shieh, T., Wu, T., Tu, M., Chen, M. Y., Yang, J."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". International Journal of Oncology 43.4 (2013): 1141-1150.
Chicago
Chang, P., Peng, S., Lee, C., Lu, C., Tsai, S., Shieh, T., Wu, T., Tu, M., Chen, M. Y., Yang, J."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". International Journal of Oncology 43, no. 4 (2013): 1141-1150. https://doi.org/10.3892/ijo.2013.2050