Obovatol induces apoptosis in breast cancer by downregulating the PI3K/Akt pathway.

IF 1.7 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2026-03-31 Epub Date: 2026-02-25 DOI:10.21037/tcr-2025-1-2627

Ling Zhang, Changyou Wei, Xin Yang, Yuting Ye, Youqin Zeng, Siyu Chen, Jiao Xia, Ping Leng

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引用次数: 0

Abstract

Background: Obovatol (Ob), extracted from the bark of Magnolia obovata Thunb., originates from a genus with a well-documented history in East Asian traditional medicine for treating ailments characterized by inflammation and neoplastic-like symptoms. Despite preliminary observations suggesting that Ob exerts anti-tumor effects in various cancers, its specific efficacy and underlying mechanisms of action in breast cancer (BC) remain largely unexplored. This study aimed to investigate the anti-tumor efficacy of Ob against BC and to elucidate its underlying molecular mechanisms.

Methods: Cell counting kit-8, Transwell, flow cytometry, and Western blotting (WB) assays were used to examine the effects and functions of Ob on cellular proliferation, invasion, and apoptosis in BC cells (MDA-MB-231 and MDA-MB-468). Bagg Albino/c (BALB/c) nude female mice were applied to evaluate the anti-cancer effects and biosecurity of Ob. Transcriptome sequencing was used to identify the pathway modulated by Ob in BC, and WB assays were then used to validate the key findings.

Results: In MDA-MB-231 and MDA-MB-468 cells, Ob decreased the cell viability, exhibiting the half maximal inhibitory concentration (IC₅₀) values for 50.97 and 48.29 µM, respectively. Additionally, by upregulating E-cadherin while downregulating N-cadherin and vimentin, Ob reversed the epithelial-mesenchymal transition, thereby significantly inhibiting the migration and invasion of BC cells. Ob led to mitochondrial apoptosis, as shown by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X protein (Bax) and activated caspase-3 levels. Consistent with the in vitro findings, Ob treatment effectively limited tumor growth in the mouse model, demonstrating considerable biological safety. Importantly, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway has been proven to be a key mechanistic target, as Ob suppressed its activation.

Conclusions: By downregulating the PI3K/Akt pathway, Ob reduced cell proliferation and invasion and induced apoptosis in BC.

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Obovatol通过下调PI3K/Akt通路诱导乳腺癌细胞凋亡。

背景：倒卵醇（obvatol, Ob）是从白玉兰（Magnolia obovata Thunb）的树皮中提取的。它起源于一个属，在东亚传统医学中有充分的记录，用于治疗以炎症和肿瘤样症状为特征的疾病。尽管初步观察表明Ob在多种癌症中具有抗肿瘤作用，但其在乳腺癌（BC）中的特异性功效和潜在作用机制仍未得到充分研究。本研究旨在探讨Ob对BC的抗肿瘤作用，并阐明其潜在的分子机制。方法：采用细胞计数试剂盒-8、Transwell、流式细胞术和Western blotting （WB）检测Ob对BC细胞（MDA-MB-231和MDA-MB-468）增殖、侵袭和凋亡的影响和功能。应用BALB/c裸雌性小鼠研究Ob的抗癌作用和生物安全性。利用转录组测序技术鉴定Ob在BC中调节的途径，然后利用WB检测验证关键发现。结果：在MDA-MB-231和MDA-MB-468细胞中，Ob降低了细胞活力，最大抑制浓度（IC50）值分别为50.97和48.29µM。此外，Ob通过上调E-cadherin而下调N-cadherin和vimentin，逆转了上皮-间质转化，从而显著抑制了BC细胞的迁移和侵袭。b细胞淋巴瘤2 （Bcl-2）水平降低，Bcl-2相关X蛋白（Bax）升高，caspase-3水平激活，表明Ob导致线粒体凋亡。与体外研究结果一致，Ob治疗有效地限制了小鼠模型中的肿瘤生长，显示出相当大的生物安全性。重要的是，磷酸肌肽3-激酶(PI3K)/蛋白激酶B （Akt）通路已被证明是一个关键的机制靶点，因为Ob抑制了其激活。结论：Ob通过下调PI3K/Akt通路，降低BC细胞增殖和侵袭，诱导凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.