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基立诺尔通过改变 PI3K/AKT 和 MAP 激酶信号通路抑制人甲状腺癌细胞的存活并诱导其凋亡。

Kirenol inhibited the cell survival and induced apoptosis in human thyroid cancer cells by altering PI3K/AKT and MAP kinase signaling pathways.

机构信息

Department of Thyroid Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.

Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

出版信息

Environ Toxicol. 2021 May;36(5):811-820. doi: 10.1002/tox.23083. Epub 2020 Dec 17.

Abstract

The thyroid cancer, especially papillary thyroid cancers are very common among population with high intake of iodine or iodine uptake. Even though several treatment options are available, there is still complication and side effects are still persistent. The role of signaling molecules in cancer signaling is very vast and their significance in progression of disease was increasing which leads to mortality of the patient. The major key players are PI3K, AKT and MAP kinase, involves in cell survival, proliferation, and inhibition of apoptosis and are the promising candidate for cancer treatment target, several researchers focuses these molecule to treat various acute and chronic diseases like cancer. On the other side, various literatures propose that natural compounds derived from plant source are shown potent anticancer property against several cancers. In our study we are looking in to one such active principle obtained from plant source, a diterpenoid compound kirenol, and its role thyroid cancer. Here, we report that kirenol role on various cellular mechanisms like induction of apoptosis, enhancing ROS indirectly by inhibiting antioxidants, altering the signaling mechanism of cell survival and apoptosis. Our study proposes that kirenol involved in the cancer cell cytotoxicity by inducing apoptosis and inhibition of cancer cell survival. Thus, targeting this signaling molecule with kirenol definitely favors and may lead to a therapeutic modality for thyroid cancer.

摘要

甲状腺癌,尤其是在高碘或碘摄取人群中非常常见。尽管有几种治疗选择,但仍存在并发症,副作用仍然存在。信号分子在癌症信号中的作用非常广泛,它们在疾病进展中的意义越来越大,导致患者死亡。主要的关键参与者是 PI3K、AKT 和 MAP 激酶,它们参与细胞存活、增殖、抑制细胞凋亡,是癌症治疗靶点的有前途的候选者,一些研究人员专注于这些分子来治疗各种急性和慢性疾病,如癌症。另一方面,许多文献提出,植物来源的天然化合物显示出对多种癌症的强大抗癌特性。在我们的研究中,我们正在研究一种从植物来源获得的活性成分,一种二萜化合物基里诺醇,及其在甲状腺癌中的作用。在这里,我们报告基里诺醇在诱导细胞凋亡、通过抑制抗氧化剂间接增加 ROS、改变细胞存活和凋亡的信号机制等各种细胞机制中的作用。我们的研究表明,基里诺醇通过诱导细胞凋亡和抑制癌细胞存活参与癌细胞的细胞毒性。因此,用基里诺醇靶向这种信号分子肯定有利于并可能为甲状腺癌提供一种治疗模式。

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