Cytotoxicity evaluation of Curcuma aromatica Salisb. rhizome extract via apoptosis and reactive oxygen species generation in human gastric cancer cells.

IF 2.9 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

3 Biotech Pub Date : 2025-06-01 Epub Date: 2025-05-06 DOI:10.1007/s13205-025-04318-1

Chinh Chung Doan, Thanh Long Le, Nguyen Quynh Chi Ho, Dinh Thach Bui, Thi Phuong Thao Nguyen, Nghia Son Hoang

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引用次数: 0

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.

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姜黄的细胞毒性评价。根茎提取物对人胃癌细胞凋亡和活性氧生成的影响。

姜黄。（C. aromatica）已被报道对不同类型的癌症具有抗增殖活性，包括结肠癌、肺癌、皮肤癌和前列腺癌。在这项研究中，我们旨在确定香根提取物（CAE）是否对胃癌细胞具有细胞毒性和凋亡作用。CAE以浓度依赖的方式抑制细胞生长，从而对不同的癌细胞产生细胞毒性作用，而在相同剂量下，CAE对正常细胞的作用最小。该提取物通过激活外源性细胞凋亡诱导胃癌AGS细胞凋亡。这种效应与死亡受体相关蛋白的上调有关，包括Fas、FasL、DR5、FADD和caspase-8。此外，它通过引起线粒体功能障碍激活内在凋亡。这与Bid表达下调、Bax/Bcl-2比值增加以及线粒体膜电位破坏有关（ΔΨm）。结果，细胞色素c被释放到细胞质中，导致caspase-9和-3的激活，随后PARP被切割。此外，通过特异性caspase抑制剂阻断caspase-8、-9和-3的活性可以保护CAE处理的AGS细胞免于凋亡。此外，CAE通过增加活性氧生成显著促进AGS细胞死亡，而活性氧被一种强效抗氧化剂NAC减弱。另外，在CAE中发现curdione， curcumenol和germacron作为潜在的活性成分。我们的研究结果表明，CAE通过激活外源性和内源性凋亡途径以及增强胃癌AGS细胞内ROS生成来触发细胞凋亡。因此，CAE可能是治疗胃癌的一种新的潜在候选药物。补充资料：在线版本提供补充资料，网址为10.1007/s13205-025-04318-1。

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来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.