梵皮酸和尤妥迪酸作为硫氧还蛋白还原酶1抑制剂,对宫颈癌具有抗增殖、抗迁移和促凋亡作用。
Antiproliferative, antimigratory, and apoptotic effects of diffractaic and vulpinic acids as thioredoxin reductase 1 inhibitors on cervical cancer.
发表日期:2023 Sep 01
作者:
Büşra Budak, Şeyda Nur Kalın, Ömer Erkan Yapça
来源:
Cellular & Molecular Immunology
摘要:
颈部癌症是女性中最常见的癌症类型之一。由于现有癌症药物的副作用和治疗方法的不足,需要寻找新的治疗靶点。硫氧还蛋白还原酶 1 (TrxR1) 经常在许多癌细胞中过度表达,因此以TrxR1为靶点已成为癌症治疗的可行方法。本研究调查了地衣次生代谢产物二氧山小车酸和戎红酸对宫颈癌HeLa细胞株的抗癌影响。通过XTT实验,发现二氧山小车酸和戎红酸以剂量依赖和时间依赖的方式抑制了HeLa细胞的增殖,相应的IC50值在48小时时分别为22.52 μg/ml 和66.53 μg/ml。这些地衣代谢物显著抑制了迁移。通过qPCR分析,二氧山小车酸显示了BAX/BCL2比值的增加,并通过流式细胞术分析证明了HeLa细胞中凋亡细胞的增加。至于戎红酸,虽然降低了这些细胞的BAX/BCL2比值,但根据流式细胞术分析结果显示增加了凋亡细胞数量。二氧山小车酸和戎红酸显著抑制了HeLa细胞中TrxR1酶活性,而未对基因和蛋白表达水平产生明显影响。本研究首次证明,利用二氧山小车酸和戎红酸靶向TrxR1是治疗宫颈癌的有效策略。© 2023. 作者,Springer-Verlag GmbH德国分公司专属许可,属于Springer Nature。
Cervical cancer is among the most frequently observed cancer types in females. New therapeutic targets are needed because of the side impacts of existing cancer drugs and the inadequacy of treatment methods. Thioredoxin reductase 1 (TrxR1) is often overexpressed in many cancer cells, and targeting TrxR1 has become an attractive target for cancer therapy. This study investigated the anticancer impacts of diffractaic and vulpinic acids, lichen secondary metabolites, on the cervical cancer HeLa cell line. XTT findings demonstrated showed that diffractaic and vulpinic acids suppressed the proliferation of HeLa cells in a dose- and time-dependent manner and IC50 values were 22.52 μg/ml and 66.53 μg/ml at 48 h, respectively. Each of these lichen metabolites significantly suppressed migration. Diffractaic acid showed an increase in both the BAX/BCL2 ratio by qPCR analysis and the apoptotic cell population via flow cytometry analysis on HeLa cells. Concerning vulpinic acid, although it decreased the BAX/BCL2 ratio in this cells, it increased apoptotic cells according to the flow cytometry analysis results. Diffractaic and vulpinic acids significantly suppressed TrxR1 enzyme activity rather than the gene and protein expression levels in HeLa cells. This research demonstrated for the first time, that targeting TrxR1 with diffractaic and vulpinic acids was an effective therapeutic strategy for treating cervical cancer.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.