Tumor Biology

, Volume 36, Issue 2, pp 633–641 | Cite as

GRP78 mediates the therapeutic efficacy of curcumin on colon cancer

  • Yu-Jia Chang
  • Chien-Yu Huang
  • Chin-Sheng Hung
  • Wei-Yu Chen
  • Po-Li Wei
Research Article

Abstract

Glucose-regulated protein 78 (GRP78) is the key regulator of endoplasmic reticular (ER) function. Expression of GRP78 was correlated with malignancy in different cancers. However, the role of GRP78 in the cytotoxic effect of curcumin on colon cancer cells is still unclear. A silencing RNA (siRNA) technique was used to knock down GRP78 expression. The anticancer effects of curcumin were assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometric cell cycle analysis, and a terminal dexynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. HT-29 cells expressed lower GRP78 compared with DLD-1 cells. The MTT assay revealed that HT-29 cells were more resistant to curcumin treatment than DLD-1 cells. GRP78KD cells showed more resistance to curcumin treatment compared with scrambled control cells. Overexpressed GRP78 in HT-29 cells increased the sensitivity to curcumin treatment. According to the cell cycle analysis and TUNEL assay, we found that apoptosis dramatically increased in scrambled control cells compared to GRP78KD DLD-1 cells after curcumin treatment. Finally, we evaluated levels of Bcl-2, BAX, and Bad and found that an increase of Bcl-2 level was observed in GRP78KD cells treated with curcumin. Those results were consistent with the increasing of resistance to curcumin after silencing of GRP78. The levels of GRP78 expression might determine the therapeutic efficacy of curcumin against colon cancer cells.

Keywords

Colon cancer Antiproliferation Curcumin GRP78 

Abbreviations

GRP78

Glucose-regulated protein 78

ER

Endoplasmic reticulum

Notes

Acknowledgments

This study was supported by grants from National Science Council (NSC101-2314-B-038-029-MY3 and NSC101-2314-B-038-016-MY3).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yu-Jia Chang
    • 1
    • 2
    • 3
    • 4
  • Chien-Yu Huang
    • 5
    • 6
  • Chin-Sheng Hung
    • 2
    • 3
    • 4
  • Wei-Yu Chen
    • 7
    • 8
  • Po-Li Wei
    • 2
    • 3
    • 4
  1. 1.Graduate Institute of Clinical MedicineCollege of Medicine, Taipei Medical UniversityTaipeiTaiwan
  2. 2.Department of SurgerySchool of Medicine, College of Medicine, Taipei Medical UniversityTaipeiTaiwan
  3. 3.Division of General Surgery, Department of Surgery, Taipei Medical University HospitalTaipei Medical UniversityTaipeiTaiwan
  4. 4.Cancer Research CenterTaipei Medical University Hospital, Taipei Medical UniversityTaipeiTaiwan
  5. 5.Division of General Surgery, Department of SurgeryShuang Ho Hospital, Taipei Medical UniversityTaipeiTaiwan
  6. 6.Department of NeurosurgeryShuang Ho Hospital, Taipei Medical UniversityTaipeiTaiwan
  7. 7.Department of PathologySchool of Medicine, College of Medicine, Taipei Medical UniversityTaipeiTaiwan
  8. 8.Department of PathologyWan Fang Hospital, Taipei Medical UniversityTaipeiTaiwan

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