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没食子酸通过调控 p-p38 和内质网应激对 PANC-1 和 MIA PaCa-2 胰腺癌细胞的凋亡作用。

Apoptotic Effect of Gallic Acid via Regulation of p-p38 and ER Stress in PANC-1 and MIA PaCa-2 Cells Pancreatic Cancer Cells.

机构信息

Department of Pathology, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul 05253, Republic of Korea.

Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul 05253, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Oct 16;24(20):15236. doi: 10.3390/ijms242015236.

Abstract

Pancreatic cancer (PC) is currently recognized as the seventh most prevalent cause of cancer-related mortality among individuals of both genders. It is projected that a significant number of individuals will succumb to this disease in the forthcoming years. Extensive research and validation have been conducted on both gemcitabine and 5-fluorouracil as viable therapeutic options for PC. Nevertheless, despite concerted attempts to enhance treatment outcomes, PC continues to pose significant challenges in terms of achieving effective treatment alone through chemotherapy. Gallic acid, an endogenous chemical present in various botanical preparations, has attracted considerable attention due to its potential as an anticancer agent. The results of the study demonstrated that gallic acid exerted a decline in cell viability that was dependent on its concentration. Furthermore, it efficiently suppressed cell proliferation in PC cells. This study observed a positive correlation between gallic acid and the production of reactive oxygen species (ROS). Additionally, it confirmed the upregulation of proteins associated with the protein kinase-like endoplasmic reticulum kinase (PERK) pathway, which is one of the pathways involved in endoplasmic reticulum (ER) stress. Moreover, the administration of gallic acid resulted in verified alterations in the transmission of mitogen-activated protein kinase (MAPK) signals. Notably, an elevation in the levels of p-p38, which represents the phosphorylated state of p38 MAPK was detected. The scavenger of reactive oxygen species (ROS), N-Acetyl-L-cysteine (NAC), has shown inhibitory effects on phosphorylated p38 (p-p38), whereas the p38 inhibitor SB203580 inhibited C/EBP homologous protein (CHOP). In both instances, the levels of PARP have been successfully reinstated. In other words, the study discovered a correlation between endoplasmic reticulum stress and the p38 signaling pathway. Consequently, gallic acid induces the activation of both the p38 pathway and the ER stress pathway through the generation of ROS, ultimately resulting in apoptosis. The outcomes of this study provide compelling evidence to support the notion that gallic acid possesses considerable promise as a viable therapeutic intervention for pancreatic cancer.

摘要

胰腺癌(PC)目前被认为是男性和女性癌症相关死亡率的第七大常见原因。预计在未来几年内,将会有大量的人死于这种疾病。吉西他滨和 5-氟尿嘧啶作为 PC 的可行治疗选择已经进行了广泛的研究和验证。然而,尽管人们一直在努力提高治疗效果,但单独通过化疗来治疗 PC 仍然存在很大的挑战。没食子酸是各种植物制剂中存在的一种内源性化学物质,由于其作为抗癌剂的潜力而引起了相当大的关注。研究结果表明,没食子酸通过其浓度依赖性降低细胞活力。此外,它有效地抑制了 PC 细胞的增殖。本研究观察到没食子酸与活性氧(ROS)的产生之间存在正相关。此外,它证实了与蛋白激酶样内质网激酶(PERK)途径相关的蛋白质的上调,PERK 途径是内质网(ER)应激涉及的途径之一。此外,给予没食子酸导致丝裂原激活蛋白激酶(MAPK)信号的传递发生了可验证的改变。值得注意的是,检测到 p38 MAPK 的磷酸化状态的 p-p38 水平升高。活性氧(ROS)的清除剂 N-乙酰-L-半胱氨酸(NAC)对磷酸化的 p38(p-p38)表现出抑制作用,而 p38 抑制剂 SB203580 抑制 C/EBP 同源蛋白(CHOP)。在这两种情况下,PARP 的水平都得到了成功恢复。换句话说,该研究发现内质网应激和 p38 信号通路之间存在相关性。因此,没食子酸通过产生 ROS 诱导 p38 途径和 ER 应激途径的激活,最终导致细胞凋亡。这项研究的结果提供了有力的证据支持这样一种观点,即没食子酸作为胰腺癌的一种可行的治疗干预手段具有很大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10607041/6b6f3606a712/ijms-24-15236-g001.jpg

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