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

Abstract

BACKGROUND:

Ginger 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.

METHODS:

Cell 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.

RESULTS:

Exposure 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.

CONCLUSIONS:

These 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.

• Authors: Gwang Hun Park, Jae Ho Park, Hun Min Song, Hyun Ji Eo, Mi Kyoung Kim, Jin Wook Lee, Man Hyo Lee, Kiu-Hyung Cho, Jeong Rak Lee, Hyeon Je Cho, Jin Boo Jeong
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 14 Pg. 408 (Oct 23 2014) ISSN: 1472-6882 [Electronic] England
• PMID: 25338635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Activating Transcription Factor 3
• Antineoplastic Agents
• Plant Extracts

Topics

• Activating Transcription Factor 3 (genetics, metabolism)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Colorectal Neoplasms (drug therapy, genetics, metabolism, physiopathology)
• Ginger (chemistry)
• Humans
• MAP Kinase Signaling System (drug effects)
• Plant Extracts (pharmacology)
• Plant Leaves (chemistry)
• Promoter Regions, Genetic
• Signal Transduction (drug effects)
• Transcriptional Activation (drug effects)