研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

通过调节Wnt / β-连环蛋白信号通路,来自天南星(Penthorum chinense)的新木脂素衍生物对人类结直肠癌细胞具有抗肿瘤活性。

Neolignan derivatives from Penthorum chinense with antitumor activity in human colorectal cancer cells by regulating Wnt/β-catenin signaling pathway.

发表日期:2023 Aug 16
作者: Mengqi Lu, Jingya Ruan, Rui Yu, Ying Zhang, Wei Zhao, Dingshan Yang, Wanxia Wang, Yi Zhang, Tao Wang
来源: PHYTOCHEMISTRY

摘要:

基于MTT实验的体外细胞毒性引导分离法对中国岩菖蒲(Penthorum chinense Pursh,石南科)进行了研究。从中国岩菖蒲的活性成分(乙酸乙酯提取物)中分离得到八种未报导过的新木脂素,命名为乙酸乙酯提取物A-H(1-8),以及两种已知的相似物(9和10)。通过实验和计算比较电子圆二色谱分析,确定了它们的绝对构型。通过MTT实验对获得的木脂素在HT29和LoVo细胞上的结果表明,之前未报导过的木脂素乙酸乙酯提取物A(1)和F(6)的细胞毒性优于阳性药物5-氟尿嘧啶。然后,通过5-乙炔基-2'-脱氧腺苷、创伤愈合、Transwell和Western blot等功能性技术,证明它们能够显著抑制HT29和LoVo细胞的增殖,通过上调Bax和下调B细胞CLL/淋巴瘤2和聚腺苷酸核苷酸聚合酶促进细胞凋亡。此外,Western blot结合Dsh同源物2激动剂IWP-L6和β-连环蛋白激动剂MG132的实验表明,它们的作用机制与抑制Wnt/β-连环蛋白信号通路密切相关。总之,之前未报导过的木脂素乙酸乙酯提取物A(1)和F(6)可能通过抑制Wnt/β-连环蛋白信号通路干预结直肠癌的发展和进展,并有潜力成为药物候选物。版权所有©2023,由Elsevier Ltd.出版。
In vitro cytotoxicity-guided isolation based on a MTT assay was conducted for Penthorum chinense Pursh. (Penthoraceae). In the active components (EtOAc extract of P. chinense), eight undescribed neolignans, penthoneolignans A-H (1-8), and two known analogs (9 and 10) were obtained and identified. Their absolute configurations were determined by experimental and computational comparison of electronic circular dichroism spectra analysis. The MTT experiment results of the obtained neolignans on HT29 and LoVo cells indicated previously undescribed neolignans, penthoneolignans A (1) and F (6), showed better cytotoxicity than the positive drug 5-fluorouracil. Then, functional technologies such as the 5-ethyny1-2'-deoxyridine, wound healing, Transwell, and Western blot assays indicated that they could significantly inhibit the proliferation of HT29 and Lovo cells, promote apoptosis by up-regulating Bax, and down-regulating B-cell CLL/lymphoma 2 and poly ADP-ribose polymerase. Furthermore, a Western blot assay combining the Dsh homolog 2 agonist IWP-L6 and the β-catenin agonist MG132 suggested their mechanism of action was closely related to the inhibition of the Wnt/β-catenin signaling pathway. In conclusion, previously undescribed neolignans, penthoneolignans A (1) and F (6), may intervene in the development and progression of colorectal cancer by inhibiting the Wnt/β-catenin signaling pathway and have the potential to be drug candidates.Copyright © 2023. Published by Elsevier Ltd.