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.
Highlights
Pancreatic cancer is a highly aggressive neoplasm with many chemotherapy- and radiotherapy-resistant phenotypes
The present study demonstrated that the extract of Syussai ginger (SSHE) had potent growthinhibitory and cell death-inducing activity against pancreatic cancer cells including Panc-1 cells
Normal cells such as Human umbilical vein endothelial cells (HUVEC) and Human pulmonary alveolar epithelial cells (HPAEpiC) were relatively resistant to SSHE compared to Panc-1 cells
Summary
Pancreatic cancer is a highly aggressive neoplasm with many chemotherapy- and radiotherapy-resistant phenotypes. Ginger extract and its pungent components, such as [6]-gingerol and [6]-shogaol, are known to exhibit many biological effects including anti-inflammation, antioxidation and anticancer activity [5, 6]. Because of its strong anti-inflammatory activity, ginger has recently drawn attention as a remedy for osteoarthritis and rheumatoid arthritis [7, 8]. With respect to anticancer activity, ginger and its constituents have been shown to inhibit the proliferation of and induce apoptosis of a variety of cancer cell types in vitro [9,10,11,12,13,14,15]. The anticancer activity of ginger extract and its constituents against pancreatic cancer has been poorly investigated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
