肉桂醛通过与 HSPD1 的共价结合诱导细胞凋亡并增强抗直肠癌活性。

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Phytotherapy Research Pub Date : 2024-10-01 Epub Date: 2023-04-22 DOI:10.1002/ptr.7840
Weiyi Zhang, Wei Lei, Fukui Shen, Mukuo Wang, Linlin Li, Junmin Chang
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引用次数: 0

摘要

结肠直肠癌(CRC)是一种常见的恶性肿瘤,在全球具有很高的发病率和死亡率。虽然手术切除和辅助放疗/化疗是治疗结直肠癌的主要方法,但由于存在耐药性强等局限性,疗效并不理想。因此,亟需新药或新的联合疗法来治疗这一患者群体。在此,我们发现肉桂醛(CA)能在 HCT-116 细胞系中发挥抗肿瘤作用。使用烷基肉桂醛探针进行靶标捕获、分子成像和活细胞追踪发现,热休克 60 kDa 蛋白 1 (HSPD1) 蛋白是肉桂醛的靶标。CA 与 HSPD1 的共价结合改变了其稳定性。此外,我们的研究结果表明,CA可通过抑制PI3K/Akt信号通路诱导细胞凋亡,增强体外和体内抗CRC活性。同时,CA与不同的化疗药物联合使用,对抗CRC药物治疗耐药的患者有益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cinnamaldehyde induces apoptosis and enhances anti-colorectal cancer activity via covalent binding to HSPD1.

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality rates worldwide. Although surgical resection and adjuvant radiotherapy/chemotherapy are the mainstays of CRC treatment, the efficacy is unsatisfactory due to several limitations, including high drug resistance. Accordingly, there is a dire need for new drugs or a novel combination approach to treat this patient population. Herein, we found that cinnamaldehyde (CA) could exert an antitumor effect in HCT-116 cell lines. Target fishing, molecular imaging, and live-cell tracing using an alkynyl-CA probe revealed that the heat shock 60 kDa protein 1 (HSPD1) protein was the target of CA. The covalent binding of CA with HSPD1 altered its stability. Furthermore, our results demonstrated that CA could induce cell apoptosis by inhibiting the PI3K/Akt signaling pathway and enhanced anti-CRC activity both in vitro and in vivo. Meanwhile, CA combined with different chemotherapeutic agents was beneficial to patients resistant to anti-CRC drug therapy.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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