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粗糙脉孢菌是一种对抗乳腺癌的潜在抗癌药物的来源。

Neurospora crassa is a potential source of anti-cancer agents against breast cancer.

机构信息

Department of Chinese Medicine, Naval Medical University, Shanghai, 200433, People's Republic of China.

Department of Chinese Medicine Oncology, Changhai Hospital affiliated to Naval Medical University, Shanghai, 200433, People's Republic of China.

出版信息

Breast Cancer. 2022 Nov;29(6):1032-1041. doi: 10.1007/s12282-022-01383-9. Epub 2022 Jul 5.

Abstract

Fungi are an excellent source of pharmaceuticals including anti-tumor agents. Neurospora crassa generates metabolites with diverse structural classes, however, its potential as an anti-tumor agent source has not been explored. The purpose of this study aimed to investigate the potential of Neurospora crassa mixture against breast cancer. The in vitro T-47D and MDA-MB-231 experiments showed that N. crassa mixture at the concentrations of both 1.7 and 0.85 µg/ml significantly inhibited tumor cell proliferation, migration and invasion, and 3D spheroid formation. However, the inhibition rates of MCF-10A ranged 10-20% at concentrations of 0.85 and 1.7 µg/ml. The mixture at the concentration of 0.85 µg/ml could significantly downregulate the expressions of transcription factors of E2F1 and E2F3, cancer stem cell-related genes of LIN28, HIWI, and CD133, and onco-lncRNA HOTAIR, and increase CASP3 activity in either T-47D or MDA-MD-231 breast cancer cell lines. In vivo breast cancer C3H mouse model results showed that N. crassa mixture significantly inhibited tumor growth. These findings suggest that N. crassa contains an antitumor component(s) against breast cancer invasiveness, which may inhibit the self-renewal and differentiation of breast cancer stem cells possibly by downregulating cancer stem cell-associated and/or transcription factor genes and oncogenes, and promoting apoptosis.

摘要

真菌是药物的极好来源,包括抗肿瘤药物。粗糙脉孢菌(Neurospora crassa)产生具有多种结构类别的代谢物,但其作为抗肿瘤药物来源的潜力尚未得到探索。本研究旨在研究粗糙脉孢菌混合物对乳腺癌的潜在作用。体外 T-47D 和 MDA-MB-231 实验表明,粗糙脉孢菌混合物在 1.7 和 0.85μg/ml 的浓度下显著抑制肿瘤细胞增殖、迁移和侵袭以及 3D 球体形成。然而,在 0.85 和 1.7μg/ml 的浓度下,MCF-10A 的抑制率在 10-20%之间。浓度为 0.85μg/ml 的混合物可显著下调转录因子 E2F1 和 E2F3、癌症干细胞相关基因 LIN28、HIWI 和 CD133 以及癌基因 lncRNA HOTAIR 的表达,并增加 T-47D 或 MDA-MB-231 乳腺癌细胞系中 CASP3 的活性。体内乳腺癌 C3H 小鼠模型结果表明,粗糙脉孢菌混合物可显著抑制肿瘤生长。这些发现表明,粗糙脉孢菌含有一种针对乳腺癌侵袭性的抗肿瘤成分(s),其可能通过下调癌症干细胞相关和/或转录因子基因和癌基因,促进细胞凋亡,从而抑制乳腺癌干细胞的自我更新和分化。

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