Abstract

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 μg/mL) and triggers cell death via caspase-dependent apoptosis in human ovarian cancer cells. Among the three major compounds isolated from the extract, 1′-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.

Highlights

  • Publisher’s Note: MDPI stays neutralOvarian cancer is the most fatal gynecological cancers around the world [1]

  • The EtOH extract of Thai ginger exhibited potent cytotoxic activity in two ovarian cancer cell lines, SKOV3 and A2780, with IC50 values below 10 μg/mL; the water extract of Thai ginger did not exert an effect on the cell viability (Figure 1A)

  • These results suggest that the EtOH extract of Thai ginger induces caspase-dependent apoptosis in human ovarian cancer cells

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Summary

Introduction

Publisher’s Note: MDPI stays neutralOvarian cancer is the most fatal gynecological cancers around the world [1]. Since there are no unambiguous symptoms, patients are mostly diagnosed at stage 3 or 4, resulting in a 5-year survival rate of approximately 30% in the past 30 years [2]. Debulking surgery and chemotherapy with taxane and platinum agents remain the standard-ofcare first-line treatments for ovarian cancer. Due to the severe adverse effects and drug resistance of taxane/platinum-based chemotherapy [3], a novel therapeutic agent that would help improve the quality of life and survival rate of patients with ovarian cancer is urgently needed. The rhizomes of A. galanga, commonly known as “Thai ginger”, have been used extensively as a spice in Southeast Asian and Arabian cuisines. The rhizomes are common ingredients in Thai curries and soups, such as tom kha kai, and used as fresh chunks, sliced, crushed, and mixed into a curry paste, or used to create a spicy with regard to jurisdictional claims in published maps and institutional affiliations

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