RRC ID 37124
著者 Akimoto M, Iizuka M, Kanematsu R, Yoshida M, Takenaga K.
タイトル Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly through Reactive Oxygen Species-Mediated Autotic Cell Death.
ジャーナル PLoS One
Abstract The extract of ginger (Zingiber officinale Roscoe) and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS) generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069) in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01) without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s) as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug.
巻・号 10(5)
ページ e0126605
公開日 2015-1-1
DOI 10.1371/journal.pone.0126605
PII PONE-D-14-54387
PMID 25961833
PMC PMC4427290
MeSH Animals Apoptosis / drug effects Blotting, Western Cell Cycle / drug effects Cell Line, Tumor Ginger / chemistry* Humans Male Membrane Potential, Mitochondrial / drug effects Mice Mice, Inbred C57BL Microscopy, Electron, Transmission Pancreatic Neoplasms / metabolism* Plant Extracts / pharmacology* Reactive Oxygen Species / metabolism
IF 2.74
引用数 56
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MIA Paca2(RCB2094) PANC-1(RCB2095)