Abstract
Curcuma aromatica Salisb. (C. aromatica) has been reported to have anti-proliferative activities against different types of cancer, including colon, lung, skin, and prostate cancer. In this study, we aimed to determine whether C. aromatica rhizome extract (CAE) exhibited cytotoxic and apoptotic effects against gastric cancer cells. CAE exerted cytotoxic effects on different cancer cells by suppressing cell growth in a concentration-dependent manner, while its effects on normal cells were minimal at equivalent doses. The extract showed induction of apoptosis in gastric cancer AGS cells via activation of extrinsic apoptosis. This effect was associated with the upregulation of proteins related to death receptors, including Fas, FasL, DR5, FADD, and caspase-8. Additionally, it activated intrinsic apoptosis by causing mitochondrial dysfunction. This was linked to a downregulation of Bid expression, an increment in the Bax/Bcl-2 ratio, and a disruption of mitochondrial membrane potential (ΔΨm). As a result, cytochrome c was released into the cytoplasm, leading to activation of caspase-9 and -3, followed by cleavage of PARP. Moreover, blocking the activity of caspase-8, -9, and -3 by specific caspase inhibitors protected AGS cells against apoptosis by CAE treatment. Also, CAE significantly promoted cell death in AGS cells via an augmentation in ROS generation, which was attenuated by a potent antioxidant, NAC. Alternatively, curdione, curcumenol, and germacrone were found in CAE as potential active constituents. Our results suggested that CAE triggered apoptosis via the activation of both exogenous and endogenous apoptosis pathways and the enhancement of intracellular ROS generation in gastric cancer AGS cells. Thus, CAE might be a novel potential candidate for the treatment of gastric cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04318-1.