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

• Published in: Tumor biology Vol. 37; no. 8; pp. 10793 - 10804
• Main Authors: Duan, Chaoqin, Zhang, Bin, Deng, Chao, Cao, Yu, Zhou, Fan, Wu, Longyun, Chen, Min, Shen, Shanshan, Xu, Guifang, Zhang, Shu, Duan, Guihua, Yan, Hongli, Zou, Xiaoping
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2016; Springer Nature B.V
• Subjects: Acetylcysteine - pharmacology; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; 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; Gastric cancer; 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; Original Article; 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; Piperlongumine; TERT; GADD45α; ROS; STAT3; CHOP; Gastric cancer
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-016-4792-9

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.