Journal
ANTIOXIDANTS
Volume 11, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/antiox11020293
Keywords
Alpinia galanga; 1 '-acetoxyeugenol acetate; ovarian cancer; apoptosis; reactive oxygen species; NADPH oxidase
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) [NRF-2019R1A2C2011213, NRF-2017R1A5A2014768]
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Thai ginger extract exhibits cytotoxic activity and induces apoptosis in ovarian cancer cells. One of the major compounds, AEA, plays a key role in the induction of apoptosis by increasing ROS levels and activating the MAPK pathway.
The rhizomes of Alpinia galanga (Thai ginger) have been used extensively as a spice in Southeast Asian and Arabian cuisines and reported to possess a wide range of biological properties, such as antioxidant, antimicrobial, and antibacterial. However, the specific molecular and cellular mechanisms underlying the anti-tumor effects induced by Thai ginger and its corresponding active compounds have been poorly characterized. We found that upon EtOH extraction, Thai ginger extract exhibits cytotoxic activity (IC50 < 10 mu g/mL) and triggers cell death via caspase-dependent apoptosis in human ovarian cancer cells. Among the three major compounds isolated from the extract, 1 & PRIME;-acetoxyeugenol acetate (AEA) exhibited potent cytotoxic activity in human ovarian cancer cells, SKOV3 and A2780. AEA induced apoptotic cell death through the activation of caspases-3 and -9. Notably, AEA enhanced the intracellular levels of reactive oxygen species (ROS), and the application of an antioxidant markedly reversed AEA-induced apoptosis of ovarian cancer cells. The knockdown of p47phox, a subunit of NADPH oxidase, suppressed both the pro-apoptotic and ROS-inducing effects of AEA. Additionally, the activation of the mitogen-activated protein kinase (MAPK) pathway by AEA through ROS regulation was found to be involved in AEA-induced apoptosis. Altogether, these results suggest that AEA exhibits potent apoptosis-inducing activity through the activation of the intrinsic pathway via ROS-mediated MAPK signaling in human ovarian cancer cells.
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