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

doi:10.1007/s13277-016-4792-9

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

Tumour Biol. 2016 Aug;37(8):10793-804. doi: 10.1007/s13277-016-4792-9. Epub 2016 Feb 13.

Authors

Chaoqin Duan¹, Bin Zhang¹, Chao Deng¹, Yu Cao¹, Fan Zhou¹, Longyun Wu¹, Min Chen¹, Shanshan Shen¹, Guifang Xu¹, Shu Zhang¹, Guihua Duan¹, Hongli Yan², Xiaoping Zou³

Affiliations

¹ Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
² Department of Laboratory Medicine, Changhai Hospital, The Second Military Medical University, Shanghai, China.
³ Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China. zouxiaoping795@hotmail.com.

PMID: 26874726
DOI: 10.1007/s13277-016-4792-9

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: CHOP; GADD45α; Gastric cancer; Piperlongumine; ROS; STAT3; TERT.

MeSH terms

Acetylcysteine / pharmacology
Animals
Antineoplastic Agents, Phytogenic / pharmacology*
Antineoplastic Agents, Phytogenic / therapeutic use
Apoptosis / drug effects
Cell Cycle Proteins / antagonists & inhibitors
Cell Cycle Proteins / physiology
Cell Division / drug effects
Cell Line, Tumor
Dioxolanes / pharmacology*
Dioxolanes / therapeutic use
Endoplasmic Reticulum Stress / drug effects
G2 Phase Cell Cycle Checkpoints / drug effects
Glutathione / pharmacology
Humans
Membrane Potential, Mitochondrial / drug effects
Mice
Mice, Nude
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / physiology
Nuclear Proteins / antagonists & inhibitors
Nuclear Proteins / physiology
RNA Interference
RNA, Small Interfering / genetics
STAT3 Transcription Factor / antagonists & inhibitors
Stomach Neoplasms / drug therapy
Stomach Neoplasms / pathology*
Telomerase / biosynthesis
Telomerase / genetics
Tumor Stem Cell Assay
X-Linked Inhibitor of Apoptosis Protein / biosynthesis
X-Linked Inhibitor of Apoptosis Protein / genetics
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents, Phytogenic
Cell Cycle Proteins
Dioxolanes
GADD45A protein, human
Neoplasm Proteins
Nuclear Proteins
RNA, Small Interfering
STAT3 Transcription Factor
STAT3 protein, human
X-Linked Inhibitor of Apoptosis Protein
XIAP protein, human
TERT protein, human
Telomerase
Glutathione
piperlongumine
Acetylcysteine