Anti-cancer activity of Ginger (Zingiber officinale) leaf through the expression of activating transcription factor 3 in human colorectal cancer cells

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.

Spices for Prevention and Treatment of Cancers

“…Besides, cysteine-conjugated shogaols, the major metabolites of shogaols in human body, exhibited similar toxicity towards human colon cancer cells [132]. In addition, the cell viability was reduced and apoptosis was induced in human colorectal cancer cells by the extracts of ginger leaf dose-dependently, and the effects resulted from activation of ATF3 promoter and following increase of ATF3 expression through ERK1/2 activation [127]. …”

Protective effect of ginger (Zingiber officinale) against PCB-induced acute hepatotoxicity in male rats

“…It has been used to treat transport and pregnancy nausea, has been used as an antioxidant, and has antimicrobial and antifungal properties, in addition to its culinary uses. 26,27 Several studies have shown that gingerol, the active ingredient of ginger, has anti-inammatory and analgesic activities. 28 Besides, "in vitro" it has been shown that Zingiber officinale has an antioxidant action and can protect against free radicals in animals, 29 hence its anticancer activity.…”

Análise Sistemática Da Produção Científica Do Zingiber Officinale Roscoe Após a Criação Da Relação Nacional De Plantas Medicinais De Interesse Ao Sistema Único De Saúde

“…O potencial anticarcinogênico do gengibre também já teve sua eficácia comprovada por inúmeros trabalhos, entre os quais se destaca um estudo in vitro, mostrando que o 6-gingerol apresenta dois tipos de efeitos antitumorais: supressão do crescimento de células de câncer de colo e a inibição do fornecimento sanguíneo ao local do tumor por meio de angiogênese (50) . Outro estudo mostrou que a redução da viabilidade celular e a apoptose em células cancerígenas de colorretal humano (HCT116) podem ser decorrentes da ação de compostos extraídos das folhas do gengibre (51) . Outra pesquisa comprovou que o extrato etanólico do gengibre reduziu significativamente o aumento da expressão do fator nuclear kappa-β (NF-kβ) e do fator de necrose tumoral-α (TNF-α) em ratos com câncer do fígado (52) .…”