Abstract
BackgroundGinger leaf (GL) has long been used as a vegetable, tea and herbal medicine. However, its pharmacological properties are still poorly understood. Thus, we performed in vitro studies to evaluate anti-cancer properties of ginger leaf and then elucidate the potential mechanisms involved.MethodsCell viability was measured by MTT assay. ATF3 expression level was evaluated by Western blot or RT-PCR and ATF3 transcriptional activity was determined using a dual-luciferase assay kit after the transfection of ATF3 promoter constructs. In addition, ATF3-dependent apoptosis was evaluated by Western blot after ATF3 knockdown using ATF3 siRNA.ResultsExposure of GL to human colorectal cancer cells (HCT116, SW480 and LoVo cells) reduced the cell viability and induced apoptosis in a dose-dependent manner. In addition, GL reduced cell viability in MCF-7, MDA-MB-231 and HepG-2 cells. ATF3 knockdown attenuated GL-mediated apoptosis. GL increased activating transcription factor 3 (ATF3) expressions in both protein and mRNA level and activated ATF3 promoter activity, indicating transcriptional activation of ATF3 gene by GL. In addition, our data showed that GL-responsible sites might be between -318 and -85 region of the ATF3 promoter. We also observed that ERK1/2 inhibition by PD98059 attenuated GL-mediated ATF3 expression but not p38 inhibition by SB203580, indicating ERK1/2 pathway implicated in GL-induced ATF3 activation.ConclusionsThese findings suggest that the reduction of cell viability and apoptosis by GL may be a result of ATF3 promoter activation and subsequent increase of ATF3 expression through ERK1/2 activation in human colorectal cancer cells.
Highlights
Ginger leaf (GL) has long been used as a vegetable, tea and herbal medicine
For the first time, we report that ginger leaves leads to transcriptional activation of activating transcription factor 3 (ATF3) which may be associated with the reduction of cell viability and induction of apoptosis in human colorectal cancer cells
Effect of GL on cell viability and apoptosis To investigate whether ginger leaf affects the cell viability in human colorectal cancer cells, HCT116, SW480 and LoVo, the cells were incubated with 50, 100 and 200 μg/ml of GL for 24 and 48 h, and cell viability was measured using MTT assay
Summary
Ginger leaf (GL) has long been used as a vegetable, tea and herbal medicine. We performed in vitro studies to evaluate anti-cancer properties of ginger leaf and elucidate the potential mechanisms involved. Gingers as perennial herbs belonging to the family Zingiberaceae have been widely used as spices, condiments and herbal medicine for treatment of cold, fever, headache, nausea and digestive problems [4]. In light of the pharmacological actions of ginger leaves, this study was performed to investigate the anti-cancer activity and elucidate the potential mechanism by which ginger leaves induces the reduction of cell viability and apoptosis in human colorectal cancer cells. For the first time, we report that ginger leaves leads to transcriptional activation of activating transcription factor 3 (ATF3) which may be associated with the reduction of cell viability and induction of apoptosis in human colorectal cancer cells
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