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树叶介导三阴性乳腺癌细胞中的DNA损伤。

Leaves Mediate DNA Damage in Triple-Negative Breast Cancer Cells.

作者信息

Cerquido Ana Sofia, Vojtek Martin, Ribeiro-Oliveira Rita, Gonçalves-Monteiro Salomé, Barroca Maria João, Moreira da Silva Aida, Viegas Olga, Freitas Victor, Sousa Joana Beatriz, Ferreira Isabel M P L V O, Diniz Carmen

机构信息

LAQV/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.

Unidade de I&D Química-Física Molecular, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.

出版信息

Curr Issues Mol Biol. 2022 Aug 11;44(8):3598-3610. doi: 10.3390/cimb44080246.

Abstract

is a shrub endemic to the Atlantic coast and has been described as yielding beneficial effects for human health. Nevertheless, studies concerning the bioactivity of leaves are scarce. This study aims at investigating the anticancer potential and mode of action, of an hydroethanolic extract of leaves (ECAL) on triple-negative breast cancer. This is a poor survival breast cancer subtype, owing to its high risk of distant reappearance, metastasis rates and the probability of relapse. The ECAL ability to prevent tumor progression through (i) the inhibition of cell proliferation (cell viability); (ii) the induction of apoptosis (morphological changes, TUNEL assay, caspase-3 cleaved) and (iii) the induction of DNA damage (PARP1 and γH2AX) with (iv) the involvement of NF-κB and of ERK1/2 pathways (AlphaScreen assay) was evaluated. ECAL activated the apoptotic pathway (through caspase-3) along with the inhibition of ERK and NF-κB pathways causing DNA damage and cell death. The large polyphenolic content of ECAL was presumed to be accountable for these effects. The extract of leaves can target multiple pathways and, thus, can block more than one possible means of disease progression, evidencing the anticancer therapeutic potential from a plant source.

摘要

是一种原产于大西洋沿岸的灌木,据称对人体健康有益。然而,关于其叶子生物活性的研究却很少。本研究旨在调查该植物叶子的水乙醇提取物(ECAL)对三阴性乳腺癌的抗癌潜力及其作用方式。这是一种生存率较低的乳腺癌亚型,因其远处复发风险高、转移率高以及复发概率高。评估了ECAL通过(i)抑制细胞增殖(细胞活力);(ii)诱导细胞凋亡(形态学变化、TUNEL检测、半胱天冬酶-3裂解)和(iii)诱导DNA损伤(PARP1和γH2AX)以及(iv)NF-κB和ERK1/2信号通路参与(AlphaScreen检测)来预防肿瘤进展的能力。ECAL激活了凋亡途径(通过半胱天冬酶-3),同时抑制了ERK和NF-κB信号通路,导致DNA损伤和细胞死亡。推测ECAL中大量的多酚成分是造成这些效应的原因。该植物叶子的提取物可以靶向多种信号通路,因此可以阻断多种可能的疾病进展途径,证明了来自植物来源的抗癌治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/386a/9406933/0f167b1fc9d3/cimb-44-00246-g001.jpg

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