Tumor Biology

, Volume 37, Issue 8, pp 10793–10804 | Cite as

Piperlongumine induces gastric cancer cell apoptosis and G2/M cell cycle arrest both in vitro and in vivo

  • Chaoqin Duan
  • Bin Zhang
  • Chao Deng
  • Yu Cao
  • Fan Zhou
  • Longyun Wu
  • Min Chen
  • Shanshan Shen
  • Guifang Xu
  • Shu Zhang
  • Guihua Duan
  • Hongli Yan
  • Xiaoping Zou
Original Article

Abstract

Recently, several studies have shown that piperlongumine (PL) can selectively kill cancer cells by targeting reactive oxygen species (ROS). However, the potential therapeutic effects and detailed mechanism of PL in gastric cancer are still not clear. In the current report, we found that PL significantly suppressed gastric cancer both in vitro and in vivo. PL obviously increased ROS generation in gastric cancer cells. Anti-oxidant glutathione (GSH) and N-acetyl-l-cysteine (NAC) can abrogate PL-induced gastric cancer cell death and proliferation inhibition. GADD45α was induced in PL-treated cancer cells and led to G2/M phase arrest, whereas genetic depletion of GADD45α by small interfering RNAs (siRNAs) could partly reverse PL-induced cell cycle arrest in gastric cancer cells. Interestingly, we also found that PL treatment decreased the expression of telomerase reverse transcriptase (TERT) gene, which plays an essential role in cancer initiation and progression. Our findings thus revealed a potential anti-tumor effect of PL on gastric cancer cells and may have therapeutic implications.

Keywords

Piperlongumine Gastric cancer ROS GADD45α CHOP TERT STAT3 

Abbreviations

ROS

Reactive oxygen species

NAC

N-acetyl-l-cysteine

GSH

Glutathione

DCF-DA

2′,7′-Dichlorofluorescein diacetate

PARP

Poly(ADP-ribose) polymerase

siRNA

Small interfering RNA

TUNEL

Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling

TERT

Telomerase reverse transcriptase

Notes

Compliance with ethical standards

Conflicts of interest

None

Funding

This study was supported by the National Natural Science Foundation of China (No. 81401974, No. 81472756, No. 81272742, and No. 81401977) and by the Natural Science Foundation from the Department of Science &Technology of Jiangsu Province (BK20140104) as well as the Outstanding Youth Project of Nanjing City (JQX14005).

Supplementary material

13277_2016_4792_MOESM1_ESM.pptx (376 kb)
ESM1 (PPTX 375 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Chaoqin Duan
    • 1
  • Bin Zhang
    • 1
  • Chao Deng
    • 1
  • Yu Cao
    • 1
  • Fan Zhou
    • 1
  • Longyun Wu
    • 1
  • Min Chen
    • 1
  • Shanshan Shen
    • 1
  • Guifang Xu
    • 1
  • Shu Zhang
    • 1
  • Guihua Duan
    • 1
  • Hongli Yan
    • 2
  • Xiaoping Zou
    • 1
  1. 1.Department of Gastroenterology, Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjingChina
  2. 2.Department of Laboratory Medicine, Changhai HospitalThe Second Military Medical UniversityShanghaiChina

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